NAB-Affective Disorders

Depression

• "common cold of mental illness"=most widespread psychological disorder
• 1/10 chance of at least one depressive episode of clinical proportions
• All population groups are vulnerable
• 1/20 visits to doctor due to depression
• >100 depressed patients per doctor's list, but half unrecognised
• 20% develop mild depression
• patients may not mention depression due to embarrassment, stigma avoid lack of sympathy
• Unipolar:
• mixed anxiety and depression
• depressive episode (single)
• recurrent depressive (numerous)
• dysthymia persistent & mild (depressive personality)
• Bipolar:
• bipolar affective disorder with manic episodes
• cyclothymia persistent instability of mood
• associated with creativity:
• Akiskal-50% major depressive illness, 70% manic depressive illness
• Schildkraut & Hirshfeld (1990)->10% cyclothymia, 40% major depressive illness

>Brain areas involved in depression: prefrontal cortex, hippocampus, nucleus accumbens & amygdala

>The longer depression left untreated, the more the hippocampus decrease in volume

>Increased metabolic activity in amygdala and orbitofrontal cortex

Is depression inherited?

>Seligman(1975)-Learned Helplessness Theory

• Dogs were placed in a two-sided box. Dogs that had no prior experience with being unable to escape a shock would jump over the hurdle in the centre of the box to land on the safe side. Dogs that learned that escape was impossible would stay on the original side, not even try to go over the hurdle.
• Animals that learned helpless show biological features of depression: REM sleep alterations, loss of body weight, diminished sexual activity elevated corticosterone.
• Cognitive function is linked to biological function through this observation
• Is it cognitive product or stress induced inactivity? 
• Recovery within 48 hours, which might be due to recovery of hypothalamic noradrenaline levels which is reduced in helpless animals

Chronic Antidepressant Treatment: 

Up-regulation of second messenger pathway

Major Classes of antidepressants & some side effects

Effects of Chronic Antidepressant Treatment on Serotonin Neurons

Neurochemical Hypotheses of Depression

1. Monoamine Theory

>Depression is due to the depletion of monoamines e.g. Noradrenaline, serotonin, dopamine which originated as drugs that depleted such as reserpine neurotransmitters

>Limitations: too simplistic, delayed action of antidepressant drugs

>Modified to include down-regulation of NA receptors

2. Noradrenaline 

>Noradregenic hypothesis-reserpine depression is due to reduced levels of NA

>supported by effects of antidepressants with increased NA metabolism

>problem: time delay of therapeutic effect

>hypothesis expanded to include receptor sensitivity

>by increased exposure of the receptor to NA eventually the sensitivity of the receptor is decreased.

3. Serotonin/5-HT

>Serotonin involved in pain sensitivity, emotionality and response to negative consequences

>Metabolite 5-HIAA (a marker for activity of serotonin) reduced in cerebrospinal fluid

>Low 5-HIAA associated with aggressive hostile and impulsive behaviour as in violent suicide attempts.

>Individuals with different alleles coding for the serotonin transporter have different reactivity to stress

The theory-Monoamine transporters

~Major mechanism controlling extracellular monoamine dynamics is re-uptake.

~This is achieved through presynaptic neurons via plasma membrane transporters

~Dopamine (DAT), Serotonin (SERT), Noradrenaline (NET)

~These remove neurotransmitters from outside cells and recycle back into releasing or neighbouring terminals.

~These transporters are targets of many psychostimulants and antidepressants, which interfere with transporter function.

~Normal function of these transporters can be studied using gene deletion technique.

~Mice lacking both SERT and DAT no place preference for cocaine suggesting SERT involvemnt in cocaine effects on reward.->SERT and DAT play a role in rewarding mechanism, lacking of them can lead to depression.

Drugs used to treat depression:

1. Tricyclics

• Inhibit re-uptake of noradrenaline and serotonin
• effective, cheap, but dose-related anticholinergic side-effects limit compliance
• often fatal in overdose

2. Serotonin selective reuptake inhibitors (SSRI's)

• inhibit reuptake of serotonin, e.g. inhibit reuptake of 5-HT and NA
• lack sedation, free of anticholinergic side effects
• narrow dose range but seem safe in overdose
• diffeent from tricyclics as little action on muscarinic cholinergics and histaminerfic receptors (will cause drowsy side-effect)

How they work

>Inhibiting the enzyme monoamine oxidase MAO that breaks down serotonin

>Blocking the transporter protein for serotonin re-uptake

The theory-Cortico-tropin-releasing factor

>CRF is a major neuropeptide mediator of stress responses in the CNS. It increases with stress level.

>It is expressed in the Paraventricular nucleus of the hypothalamus and coordinates the release of adrenocorticotropin hormone (ACTH) from the anterior pituitary.

>CRF is high in CSF of depressed patients. (up to 6 times)

>HPA axis-Hypothalamic Pituitary Adrenocortical system

• CRF is released in response to environmental stressor (uncertainty arousal).
• ACTH is then released by the pituitary.
• Cortico-steroids are released
• When stressor terminated-negative feedback occurs, shut down of the HPA axis.

>Corticosteroids elevate in times of threat and at times of loss of control

>transcient (short-term) activation does not cause stress

>excessive long-term activation of HPA may induce long-term damage

>Depression is associated with increased activity of the HPA axis, results in enlargement of adrenal gland with elevated levels of cortisol.

>antidepressants lower activity in the HPA axis.

>Early experience (maternal separation) can bias towards later protracted activity of the HPA

>Corticosteroids are given for arthritis and cause depression

>Reuptake inhibitors boost the HPA system. Improvement in mental state associated with normalisation of HPA activity.

>Cushings Disease which involves excessive secretion of corticosteroids is commonly followed by depression.

Neurogenesis:

> Neurogenesis (new neurons generated) occurs throughout life in hippocampus & olfactory bulb.

>In rodent brain studies 9k new cells/day or 250000 new cells/month in adult, 50% became neurons

>Factors affecting neurogenesis:

• increase: exercise, environmental enrichment, antidepressants
• decrease: stress, sleep deprivation, age

NAB-Reward, pleasure and desire

Reward=object/event that elicits approach and is worked for.
It is associated with wanting and liking.
Wanting=feeling of desire and approach behaviours
Liking=feeling of pleasure (explicit liking) and other objective responses (implicit liking)
Alterations in the brain substrates of reward-related processes are likely mechanisms underlying addiction.

Classical techniques to identify brain substrates of reward:

Nucleus accumbens

In rats:

Rewarding stimuli increase dopamine transmission in NAC, animals work to increase dopamine stimulation within NAC, and dopamine antagonists block behavioural effects of rewards.
NAC dopamine causes pleasure and desire.

Similarly, in humans, nucleus accumbens dopamine release during reward anticipation.

>In the Meso-corticolimbic dopamine system:

• rewards increase NAC dopamine
• systemic and intra-NAC dopamine antagonists block responses normally maintained by reward

>Cholinergic projection from PPTg to VTA:

• electrical self-stimulation
• Cholinergic drugs are self-administered into VTA

>Glutamate projections from mPFC to VTA:

• electrical self-stimulation
• stimulate dopamine release in NAC

How much one works for reward may not directly reflect the liking or pleasure induced by the reward, but rather wanting of or desire for the reward.

Overlap between brain substrates of positive and negative emotions:

Brain substrates of emotional states associated with aversive stimuli and appetitive stimuli habe originally been studied seperately, but more recently it has come to the fore that there is an overlap.

• Dopamine and nucleus accumbens play important roles in fear-related processes, in adition to loe in reward-related states and responses.
• Amygdala, apart from playing key role in fear-related responses, ahs also been implicated in responses to appetitive stimuli.

A common currency of emotoion may enable brain to generate adaptive responses baed on integrated assessment of positive and negative stimuli.
Brain substrates such as dopamine, nucleus accumbens and amygdala may not play specific role in emotion per se, but may contribute to fundamental cognitive processes that are associated with both aversive and appettitive stimuli (e.g. salience signalling and attention or associative learning).

NAB-Fear and Anxiety

Fear and anxiety comprise protective/defensive responses normally elicited by aversive stimuli.
Much animal research on brain substrates of emotion over the last 30 years has focused on fear and anxiety.

Fear=phasic escape or avoidance responses to distinct aversive stimuli.
Anxiety=tonic response to diffuse aversive situations and is associated with conflict and uncertainty.

There are many types of fear and anxiety responses, the brain substrates of these different responses may differ.
Fear- and anxiety-related disorders in humans include generalised anxiety disorder, obsessive-compulsive disorder (OCD), panic disorder, phobias, and post-traumatic stress disorder(PTSD).

Amygdala

Lesions in amygdala affect the fear conditioning. Lateral and central amygdala having lesions would reduce fear response greatly.

The role of the amygdala in conditioned fear has been very well characterised, however other brain structures e.g. hippocampus, prefrontal cortex may also make important contributions to fear and anxiety, and the substrates of conditioned fear may differ from those of other fear/anxiety-related behaviours.
Amygdala is also involved in other emotional and behavioural processes.

Hippocampus

Hippocampal lesions increase the time rats spent in the open arms of the elevated plus-maze: hippocampal lesions reduce anxiety.

SO...

Is it necessary to refer to subjective feelings if we want to study brain substrates of emotions?
What advantages and disadvantages does it have to study neural mechanisms of emotion without reference to subjective feelings?
How can we study brain substrates relevant to fear/anxiety in rat models?
How can we confirm that similar brain substrates are also important for human fear/anxiety?

Emotional responses can be measured objectively, enabling the scientific study of emotions in animals.
In animal experiments, the measurement of emotional responses can be combined with a variety of techniques to manipulate and monitor brain function in order to reveal brain substrates of emotions and their dysfunctions.
The detailed information from animal experiments can be confirmed by appropriated research on human emotions in healthy subjects and clinical populations.

Of course, human emotions cannot be explained fully through animal studies; but a good understanding of some basic emotional mechanisms that are common to humans and other animals has already been formed.
The interaction between newly evolved functions i.e. language and consciousness, and emotions could be studied.

NAB-Emotion

Emotions are states elicited by rewarding or aversive stimuli (S+ or S-) and their omission(-) or termination(!).

These states comprise thoughts and physiological/behavioural responses to emotional (i.e. rewarding or aversive) stimuli.

The physiological/behavioural responses to emotional stimuli can unambiguously be measured in human and non-human animals.

These physiological/behavioural responses to aversive and positive stimuli have fundamental survival value and, therefore, have been relatively preserved throughout evolution and are very often very similar in different animals including humans.

With the similarities between species, we can study emotions in animals and generalise it.

E.g. using rats as a model system:

>Advantages-easy to breed and keep, well-established behavioural tests, brain large enough to apply selective manipulations to distinct brain structures and brain anatomy very well characterised.

>Disadvantage-difficulty in genetic manipulations->alternative=mouse

Hippocampus, amygdala & hypothalamus:

-Papez theory of emotion (1937)

-Kluver and Bucy's description of temporal lobe lesion effects in monkeys (1939)

-Maclean's limbic system theory (1949)

Prefrontal cortex:

-Case of Phineas Gage described by Harlow (1868)

-Nauta (1971): Frontal lobes and interoception

Meso-corticolimbic dopamine system:

-Olds and Milner (1954): Brain-stimulation induced reward

-Wise et al. (1978): Neuroleptic-induced anhedonia

NAB-Cytoarchitectonics

Cytoarchitecture (Greek κύτος= "cell" + αρχιτεκτονική= "architecture"), also known as cytoarchitectonics: study of the cellular composition of the body's tissue under the microscope.

Microscopic anatomy: Brodmann areas   

• brain segmented according to appearance in microscope (cytoarchitectonics)
• combined with comparative neuroanatomy
• appearance reflects type of cells (e.g. inputs vs outputs)
• type of cells sometimes correlates with function
• studies restricted to small number of brains

Neuroscience methods for physiological psychology

Aim: to study relationship between brain and behaviour

1. Neuroanatomical & Neurochemical methods:

• Cytoarchitectonics (Brodmann areas)-study of cellular composition of the body's tissues under the microscope
• staining, immunocytochemistry & autoradiography

2. Recording & stimulating neural activity:

• non-invasive methods to study living human brain-TMS, EEG, ERPs and fMRI
• micro- and macro-electrodes in animal studies

3. Effects of brain lesions:

• pathology leading to human brain lesions
• virtual lesions induced by TMS
• experimental ablation in animal models with stereotaxic guidance)
• cooling induces reversible lesion

Neuroscience techniques-serving for study of relationship between brain and behaviour
Is there any ideal method that spatial resolution=cellular level, temporal resolution=millisecond scale,  study the whole brain simultaneously and being non-invasive at the same time? NO!
Match existing methods, which all of them come with certain limitations, to the research question.




How to us electrophysiolocial methods for cognitive neuroscience?
>responses to multiple repeated events occurring with fixed latency (time-locked)
>non-time-locked responses to events (oscillations of specific frequency)
>Events are experimentally controlled, e.g. a sensory stimulus or a task instruction occurring at a defined time point

NAB-Transcanial magnetic stimulation (TMS)

TMS:

• Non-invasive, painless, safe stimulation of human brain cortex (through the skull)
• useful in studying behaviour during virtual brain lesions, chronometry and functional connectivity
• could administered as single pulse or repetitive TMS
• stimulater in the shape of 8 placed above the scalp, contains a coil of wire->brief pulse of high electrical current fed through the coil magnetic files in lines of flux formed perpendicular to the plane of the coil, into the skull->magnetic field induces electric filed perpendicular to magnetic filed-> electric field leads to neuronal excitation trans-canially (within the brain)
• effect depends on stimulation site

>>How to measure the effects of TMS:

• Motor cortex stimulation
• activates corticospinal neurons trans-synaptically (occurring or existing across a nerve synapse)
• e.g. TMS coil 5 cm lateral from vertex (highest point)->often contralat' thumb twitches (20 ms post TMS)
• record motor evoke potential (MEPs)* (surface EMG, target muscle relaxed)
• record silent period* in contracted target muscles~150 ms after motor cortex stimulation, cortical mechanisms
• Occipital cortex stimulation:
• excitatory effects: e.g. phosphenes*; inhibitory effects: suppression of motion perception and letter identification
• Somatosensory cortex stimulation
• may elicit tingling, block the detection of peripheral stimuli (tactile, pain)
• can modify somatosensory evoked potentials (SEPs)
• Auditory cortex stimulation: 
• Interpretation of results challenging: loud coil click
•  Frontal cortex stimulation
• Effects on subject's mood? Potential for therapeutic use?

*MEPs=the electromyograph** responses of the peripheral muscles to electrical stimulation to the motor cortex. Changes in the MEP signal have been shown to exhibit significant correlation with neurological deficit and spinal cord injury.
**Electromyograph (EMG)=electrodiagnostic medicine technique for evaluating and recording the electrical activity produced by skeletal muscles, performed with an instrument- electromyograph to produce a record called electromyogram.
*Silent period=MEG silence after MEP
*Phosphenes=a ring or spot of light produced by pressure on the eyeball or direct stimulation the visual system than by light.

TMS application: cross modal plasticity

>Blind people can learn to read Braille, compared to sighted people they have superior tactile perception. Is there any underlying changes in the brain?
>Their visual cortex is known to be activated during Braille reading, is there functional significance of this activation?->TMS
>Chronometry-timing of mental events

• single pulse TMS for mental chronometry
• early blind subjects: blind before 1 year old
• real & nonsensical Braille stimuli presented via tactile stimulator
• interval between tactile stimulus (Braille) and TMS systematically varied
• subjects have to detect stimuli and identify if they are real or nonsensical
• DV: number of correctly detected/identified stimuli
• Conclusion: visual cortex contributes to tactile information processing in early blind subjects=crossmodal plasticity

*Different symbols (square, triangle, circle) representing different subjects.

*Open symbols=detected stimuli; filled=correctly identified stimuli

TMS application: virtual lesions

>Repetitive TMS can create temporary inhibitor of brain areas, fully reversible virtual lesions (for a few minutes, subjects behave as if after a brain lesion)

>errors during Braille reading by early blind and sighted subjects depend on site of virtual lesions

>cross modal plasticity in early blind subjects stated that occipital cortex supports Braille reading

>for sighted controls, max error rate after anterior parietal virtual lesion

>for early blind subjects, max error rate after occipital virtual lesion

TMS Advantages & Disadvantages:

• Advantages:
• temporal resolution in millisecond range
• virtual lesion in subject may be better defined than lesion in patient
• short duration of experiment minimises risk of plasticity
• repeated studies in the same subject
• group studies with standardised experimental setup
• study double dissociations: stimulate or temporal disrupt different cortical regions during one task, one region during different tasks
• Disadvantages:
• spatial undersampling(only one area at a time)
• only cortical area accessible
• auditory cortex stimulation problematic (muscles)
• loud coil click, need 'sham stimulation'

Stats-Questionnaire Design

Types of research/practice:

• Individual differences-psychological traits/characteristics
• Ability-Intelligence tests
• Attitudes-Measure particular beliefs toward something

**Ethics/moral: These tests are now used so widely, it is important to assess that they are reliable and valid that they are measuring what they claim to measure. The test should be ensured to avoid biases, and everyone has an equal opportunity of understanding the tests.

Creating your questionnaire

1. Question formats

• Open format questions
• asks for some written detail, but has no determined set of responses
• Advantages: leads to more qualitative data
• Disadvantages: time consuming to analyse 
• Closed format questions
• short questions or statements followed by a number of options.

2. Theoretical literature

• Theoretical literature: ideas that appear in the theoretical literature should be used as a basis
• Experts: recruit experts in the area to suggest items
• Colleagues: brainstorming to generate more items

3. Clarity of questions

• questions must be clear, short and unambiguous 
• the psychometric test question must not mean different things to different respondents

4. Avoiding leading questions

• the question should not be leading the respondent in particular direction by potentially excusing the behaviour

5. Reverse wording

• how to encourage the participant to read each question, not just get into a pattern of responding to all the questions in the same way.
• reverse wordings allow people to really pay attention

6. Response formats

• dichotomous scales: yes/no true/false
• frequency: always/sometimes/never scale
• attitude scales: strongly agree-strongly disagree
• numerical sales: to what extend the statement describes you

7. Instruction

Classical theory of error in measurement

OBSERVED score=TRUE score+ERROR

-Any score on a test for an individual on any occasion differs from his true score on account of random error.

-If we were to test an individual on many occasions, a distribution of scores would be obtained around his true score. The mean of this distribution, which is assumed to be normal, approximates the true score.

-The true score is the basis of the standard error of measurement. Thus, if we find that there is a large variance of obtained scores for an individual, there is clearly a considerable error of measurement. Since the test-retest reliability is the correlation between the obtained scores on two occasions, it is obvious that the higher the test-retest reliability, the smaller the standard error of measurement, according to this model.

-The classical theory of error assumes that any test consists of a random sample of items from the (hypothetical) universe of items relevant to the trait.

-So the most important point is that in any measurement, there is likely to be some error involved, but in order to make a good questionnaire, we want to minimise error, and to do this we maximise reliability and validity.

Reliability-we are interested in consistency

1. Internal-To what extent do the individual items that make up a test or inventory consistently measure the same underlying characteristic?

• A questionnaire having high internal variability is that all of the questions hand together and measure the same thing.
• The higher the number of resulting coefficient, the more the data are close to each other, the better it is.
• Split-half reliability: split the data into two halves, if the test is reliable, there should be a high correlation between in scores between the two halves of the test.
• Parallel forms: creating a large pool pf items that are measuring the same thing, administer to the same group of participants with interval and counterbalancing. 
• Cronbach's Alpha: mathematically equivalent to the average of all possible split-half estimates, values up to +1.00, usually a figure of +0.70 or greater indicates acceptable internal reliability
• Kuder-Richardson Formula 20(KR-20): measures internal reliability for measures with dichotomous choices (yes/no), values up to +1.00, usually a figure of +0.70 or greater indicate acceptable internal reliability.

2. External-To what degree does a person's measured performance remain consistent across repeated testings?

• test-retest reliability (stability over time): perform the same survey, with the same respondents at different points in time. The closer the results, the greater the test-retest reliability of the survey. The correlation coefficient between the two sets of responses is often used as a measure of the test-retest reliability.

3. Inter-rater reliability (or agreement)

• determines the extent to which two or more raters obtain the same result when coding the same response
• Cohen's Kappa: values up to +1.00, larger numbers indicate better reliability, used when there are two raters
• Fleiss' Kappa: an adaptation which works for any fixed number of raters
• Measures agreement, not accuracy

4. Intra-rater reliability (or agreement)

• The same assessment is completed by the same rater on two or more occasions. These different ratings are then compared, generally by means of correlation.
• Since the same individual is completing both assessments, the rater's subsequent ratings are contaminated by knowledge of earlier ratings.

**Sources of unreliability: guessing, ambiguous items, test length, instructions, temperature, illness, item order effects, response rate, social desirability

Validity-if it measures what it claims to measure

1. Faith

• simply a belief in the validity of an instrument without any objective data to back it up, and the evidence is not wanted.

2. Face

• If something has face validity, it looks like a test that measures the concept it was design to measure. The more a test appears to measure what it claims to measure, the higher its face validity.
• Face validity bears no relation to true validity and it is important only in so far as adults generally will not so-operate on tests that lack face validity, regarding them as silly or insulting. Face validity then, is simply to aid cooperation of subjects.

3. Content

• The extent to which a measure represents all facets of the phenomena being measured

4. Construct

• Seeks to establish a clear relationship between the construct at a theoretical level and the measure that has been developed.
• Convergent validity: That the measure shows associations with measures that is should be related to.
• Discriminnant validity: That the measure is not related to things that it should not be related to.

5. Predictive

• Assesses whether a measure can accurately predict future behaviour.

Stats-Threats to validity

In an experiment, we identify cause-effect relationships:

~we control the cause and observe the effect.

~changes in the DV caused by the manipulation of the IV.

Internal Validity

=>The extent to which the results obtained are a function of the variables that were systematically manipulated. Are changes in the IV responsible for the observed variation in the DV? Might the variation in the DV be attributable to other causes (confounds)?

=>Why is it important?? High internal validity=strong evidence of causality

=>To maximise internal validity:

• must be able to rule out the possibility of other factors producing the change(confounds)
• must control everything and eliminate possible extraneous influences
• easient in highly controlled, laboratory settings

=>Threats to internal validity that compromise our confidence in saying that a relationship exists between the IV and DV:

• History effects-events occurring during the experiment that are not part of the treatment; can be solve by holding experiences constant except for IV/randomlyy assign conditions to time
• Maturation effects-bilogical or psychological processes (e.g. aging, fatique, hunger...) within partcipants that may change due to the passing of time
• Mortality-differential loss of individuals from treatment and/or control groups due to nonrandom reasons (those who drop out of a study could be qualitatively different from those who remain)
• Instrument decay-equipement becomes iaccurate with age/experimenters become more skilled or bored; can be solve by randomisation condition to time, check reliability of instrument and staff.
• Participant selection-different types of participants placed at different levels of the IV; use random assignment or matching method
• Statistical regression to the mean-going back to mean after extreme behaviour
• Participants communicate-diffucion of treatment effects (control group learns about the manipulation), compensatory rivalry (participants in different conditions start competing), compensatory equalisatoin (experimenters know the condition of participants are in and provide enhance services that go beyond the routine), resentful demoralisation (control group leans that they are in the control and not try as hard)

External Validity

=>Does the IV represent the concept we intend? A measure is externally calid if it truly measures the hypothetical construct intended. An experiment is externally valid if it is similarto phenomenon in the real world.

=>Having high external validity often means having a lack of contrl of confounds

=>Population validity: the extent to which the results can be generalised from the experiemntal sample to a defined population

=>Ecological validity: the extent to which the results can be generalised from the set of experimental conditions in the experiment to other conditions.

=>Threts to External Validity compromises our confidence in stating whether the study's result are generalisable:

• reactive effects of testing: when a pre-test increase/decrease the repondents' sensitivity to the treatment (especially in seld-eport measures of attitude and interest)
• reactive effects of experimental setting: when the conditions of the study are such that the results are not likely to be replicated in the non-experimental situation
• selection-treatment interaction: the possibility that some characteristic of the participants selected for the study enteracts with some aspect of the treatment (prior experiences, learning, personality factors...)
• multiple-treatment interference: participants receive more than one treatment, the effects of previous treatment may influence subsequent ones (sequence effects/carry-over effects)

=>Improving External Validity:

• Replication-an additional scientific study conducted in exactly the same manner as the original research project. When we replicate an experimental finding, we are able to place more confidence in that result.
• Replication with extension-seeks to replicate a previous finding but does so in a different setting /with different participants/under different conditions

Statistical Validity

=>Making type 1 error: rejecting the null hypothesis when the null hypothesis is true (false positive)

• possible causes: fishing

=>Making type 2 erroe: failing to reject the null hypothesis when the null hypothesis is false (false negative)

• possible causes: power, reliability of measures/ =treatments, random irrelevance, random heterogeneity of respondents...

Stats-Experiemntal Design

What is an experiment?
Oxford English Dictionary: A scientific procedure undertaken to make a discovery, test a hypothesis or demonstrate a known fact.

Experimental vs. Non-Experimental Research

Experimental Research:
-investigates causality
-manipulate IV to determine if it has an effect on the DV
-hold other variables constant

Non-experimental Research:
-observe and measure only descriptive
-investigates correlation/associations

True vs. Quasi Experiments

-True experiments randomly allocate participants to conditions.\

-Randomization: Each participant has an equal chance of being allocated to any condition.

-Why randomize? To reduce the chance of other variables (confounding oor nuisance variables) changing the outcome. Randomisation worksby spreading any potentially confounding variables evenly accross conditions. It minimizes systematic differences to isolate the causal effects of the treatment on the dependent variable.

-If it is not possible to radomise then a quasi-experiemental approach is used. Quasi-experiments do not use randomization. Also called 'natural experiments'.

-Types of Quasi-experiment:

1. One group pre-post test design: only treatment group, often used in audits to evaluate clinical services but outcomes may be due to other factors.

2. Non-equivalent control group design: A control group is used but randomisation is not. This means conrols are systematically different from the treatment group

3. Interrupted time series design: Do not alys have a control group, good for studying naturally occuring chronological data.

Systematica approaches to control for confounding:

1. Blocking/Randomised Block Design

>Used when a variable might have a particular influence on the outcome.

>Arrage the participants into groups (blocks) according to that variable.

>Randomized the participants within those groups to the treatment group.

>E.g. Gender

2. Matching/Matched-subjects/matched case-control design

>A statistical technique where every participant is compared with another participant who is matched according to a relevant confounding variable.

>E.g. Age, IQ

3. Counterbalancing

>In a within-subjects design the outcome may be affected by the testing order. Counterbalancing can be used to compensate.

>Latin Squares counterbalancing method is used with more than one condition/treatment. Testing is arranged so each condition occupies each rank in the testing order equally often.

Stats-Ethics

Ethics--Moral principles that govern a person's behaviour. (Oxford English Dictionary)

How do you make ethical decisions? Are you a deontologist or consequentialist?
Deontological (duty based): You have a duty to do the right tihing regardless of the consequences.
Consequential (outcome based: Choose the action that maximise good consequences.
     -Utilitarinism: maximise well-being for the most people.
     -Hedonism: maximise pleasure
In practice, people tend to use a mix of deontological and consequential ethics.

The British Psychological Sciety (BPS) Guidelines respects for autonomy and dignity, approving researches according to harm avoided, risk assessed informed consent and debriefing.
In the UK, strct laws require animal researchers uses the three Rs:
1. Refinement: reduce the severity of inhumance procedures
2. Reduction: in numbers of animals used
3. Replacement: of highly sentient animals whenever possible.

NAB-Learning and memory systems

Retrograde and Anterograde Amnesia


Causes of Anterograde Amnesia:

• Alzheimer's disease (also short term memory deficits and confusion)
• Korsakoff's psychosis (RA too, maybe reflecting gradual onset, confabulation)
• Herpes encephalitis
• Anoxia/ ischaemia (can result in very selective AA)*
• Injuries or tumours to limbic system and/or diencephalon (i.e. thalamus & hypothalamus)
• Surgeries for epilepsy involving temporal lobe(s)
• Degenerative brain diseases (e.g. schizophrenia, advanced multiple sclerosis, Huntington's disease)

*Damage to Field CA1 caused by Anoxia:(a) Section through a normal hippocampus. (b) Section through the hippocampus of patient G. D. The pyramidal cells of field CA1 (between the two arrowheads) have degenerated.

>>The case of H.M. (Milner et al., 1968)
-Generalised epileptic seizures
-Bilateral medial temporal lobe resection
-Severe AA
-Above average IQ
-Normal on perceptual tests
-Good memory for events prior to surgery and early life history
-While at the research centre, HM repeatedly asked where he was and how he came to be there.
-Compared with a few other cases with restricted limbic and/or temporal lobe damage: they all have reasonable IQ, intact STM, but very poor LTM for new material, and intact perceptual/motor learning

The Claparede Effect: When Claparede went up to a patient with a pin in his hand when they shook their hands, the pin would hurt her. Everyday Claparede greets the lady and she could not recognise him at all time, however, when he offered to shake, she hesitated, recognising a threat despite her memory has been severely damaged.

The nature of the deficit:

1. Selective effect on LTM, but STM or WM intact.
     >Normal working memory on digit span-usually 7+3 digits
     >Extended digit span-multiple repetitions of same digit string can increase the span, usually up to 20
     >HM could not recall any string in excess of his normal ST span, even after 25 repetitions of the same string
2. Global-impairments across different modalities and materials
     >Various tests conducted on patients to assess their learning and memory (e.g. free recall, cued recall, recognition...)
     >Amnesia seen for information presented in different modalities (e.g. visual, auditory and olfactory)
3. Selective-only impairments in remembering new facts and events
     >HM is unable to report any personal or public events since time of surgery
     >Impaired on list-based tasks (e.g. paired associate learning)
4. Selective-amnesia spares learning and expression of skilled performance
     >Amnesics' performance in repetition priming (e.g. picture fragment completion, word stem completion) improved by experience
     >Amnesics showed savings in mirror tracing task (reproducing outline with only visual information from mirror)
     >Amnesics get fast and accurate with multiple presentations in mirror-image reading task
     **Spared skilled and performance but have little or not memory for learning experience, little recall/recognition of test materials, little or no insight into skills acquired (typically unaware that performance has improved)
5. Information that can be learned is inflexible and can only be expressed in limited contexts
     >Performance has to be measured in exactly the same way to show savings
     >Facilitation does not carry over to other tasks or test contexts

Hypotheses arising from the human clinical literature based on preserved abilities in cases otherwise severely amnesic:
=>Ryle (1949)-A number follow the distinction from philosophy between knowing how and knowing that.
=>Squire (1992)-Procedural vs declarative memory
=>Tulving (1972)-Semantic vs episodic memory

Two(or more) memory systems?
~Wider circuitry, not just hippocampus, involved in declarative or episodic processing
~Relatively pure amnesia also results from damage to mamillary body


Studies of AA confirm the distinction between long-term and working memory & implicit and explicit learning.
Learning and memory affected in amnesia seem to require hippocampus and/or related structures.
But the hippocampus cannot be the storage site for LTM, neocortex?
Intrusions errors evidence suggests material is in memory somewhere but appropriate retrieval is problematic. Lost/reduced encoding specificity?

NAB-Mechanisms of Classical Conditioning

Unconditioned Stimulus (UCS): elicit a response automatically

Conditioned Stimulus (CS): previously a neutral stimulus, elicits a conditioned response after being associated with a UCS

E.g. Eyeblink conditioning in rabbits->association between sound and puff of air

>Sound+puff of air=blinking

>Sound=blinking

But, what are the rabbits learning? S-R associations (sound=blinking)? S-S associations(Sound=puff of air)?

Most often S-S associations, but S-R associations are also possible.

The events to be associated need to be paired in time so that they occur together:

"Two ideas will be associated if they occur closely together in time." (Hume, 1700s)

"Cells that fire together, wire together." (Hebb, 1949)

Second-order conditioning:

>CS1=US

>CS2=CS1

>CS2 will elicit the CR

Sensory preconditioning:

>CS1=CS2

>CS2=US

>CS1 will elicit the CR

Pavlov's theory of temporal contiguity where he drew conclusions from over 7000 conditioning experiments:

• The CS and UCS must come into temporal contiguity
• They must do so repeatedly
• Time is fundamental in CC
• Best conditioning: when the CS is followed by the US

Different ways to present CS and US in time:

1. Delay Conditioning-US is presented after CS
2. Trace Conditioning-CS and US are separated by a gap
3. Simultaneous Conditioning-CS and US are presented at the same time
4. Backward conditioning-US is presented before CS

Temporal contiguity generally improves learning. But not always.

=>Berstein's Taste aversion study (1978):

• Group of patients where the chemotherapy they have to undergo causes nausea.
• A new taste of ice-cream, Mapletoff was given to the conditioning group of patients one hour before treatment.
• They rejected Mapletoff ice-cream later.

Studies of trace conditioning show that temporal contiguity between CS and US is generally important, but the study of taste aversion show that temporal contiguity is not necessary for successful associative learning.

So, does the role of temporal contiguity depend on the importance of other factors too?

Overshadowing: effects of stimulus intensity

-Overshadowing: Two CS are paired together with a US. The strength of conditioning to each CS individually is weak

-Conditioned suppression: Decrease in response for reinforcement after the presentation of  a CS which predicts something aversive. Less conditioning= high suppresion ratio

Latent Inhibition

Phase 1) Pre-exposure: CSa=nothing, control: CSb=nothing

Phase 2) Pre-exposure: CSa=US, control: CSa=US

~Stimulus pre-exposure in ohase 1 reduces later learning in ohase 2 when the stimulus is now relevant

~LI can apply to both exitatory and inhibitory stimuli

Conditioned Inhibition: Inhibitory Learning

-When the CS is associated with the absense of the US where phase 1: CS1=US, phase 2: CS1+CS2=nothing

-Excitor and inhibitor neutralizes out each other

-When the inhibitor is later matched with a US, learning is slower

Blocking

-Prior conditioning with a CS1 blocks conditioning with a CS2 when they are presented together

-Learning occurs when the CS provides new information about the US.

-If the second CS2 predict something new, learning should occur. In group 2, CS2 predicts a new strong shock, rats learn the association between CS2 and the new shock.

-Some cues are redundant.

Relative validity

-In correlated group, A and B are bettwe predictors of the US than X. 

-In uncorrelated group, A and B are bad predictors of the US, but when the US is present X was always present.

-More conditioning to X in the uncorrekated group. Subjects learn about the best predictor.

-Some stimuli could be poorly correlated with outcomes.

NAB-Categorisation

Concepts are not always defined by specific features, sometimes concepts do not have necessary or sufficient features to define them.

Types of Concept:

1. Basic level concept--based on similarity of perceptual qualities

2. Superordinate concept--groups of basic level concepts; not based on perceptual similarity

3. Abstract concept--does not refer to individual entity, but to some property, relation or state

SO... Can animals form basic level concepts? superordinate concepts? abstract concepts? If yes, how they do it? Do animals form concepts in the same way as humans?

=>Bhatt, Wasserman, Reynolds & Knauss (1988)-pigeons were trained to peck different keys for exemplars of each category of item presented. When new exemplars are tested with, they were able to respond correctly with an accuracy of 60% than the 80% of trial items. This suggests that the pigeons had formed a concept of the tested items.

Theories of basic level concept formation:

i) Exemplar theory: Learn about every instance independently. Classify novel exemplars on the basis of similarity to learned instances

--Animals are more accurate with the novel test stimuli as they are storing information about the training exemplars.

ii) Prototype theory: Abstract a prototype that corresponds to the central tendency of training exemplars. Classify novel exemplars on basis of similarity to new prototype.

--Human categorize the prototype more accurately than th etraining stimuli, even if it has never been encountered before.

SO do animals and humans store concepts in different ways? 

=>Aydin & Pearce (1994)-trying to show a prototype effect in animals. The birds learned that three positive patterns were always paired with food, where the three negative patterns were not. Birds pecked more at positive than negative patterns. When one of the three elements in a set is subsituted by an element from the other set, the birds responded more to the typical +ve patterns than the substituted ones, and less to the typical -ve patterns than the substitued ones. It was an evidence of protitype effect.

SO do humans store examplars as well?

=>Whittlesea (1987) created 3 lists of 5 words accordig to a prototype where all 3 lists differ from the prototype by 2 letters, but list 1 is more similar to list 2 than list 3. Paticipants studied list 1 and were tested with all 3 lists. If they have abstracted the prototype, then they should be uqually good at categorising the lists (randomly) as they all differ from the prototype by 2 letters.

But if they are remembering exeplars, then list 1 should be the easiest (studied), then list 2 (differs a little from 1) and 3 (differs a lot from 1).

**Humans show results consistent with th exemplar theory.

Both humans and animals retain information about the training items/exemplars. The prototype theory turns out to be explainable by a variation of examplar theory!

If the exemplar theory assumes that each stimulus comprises a set of component feature that are associated with category membership, then it can explain the prototype effect.

The exlanation is viewed as a new theory: "feature theory".

Feature theory and exemplar theory both say that you store something about the stimuli on each trial. 

Exemplar story says that new stimuli are classified based on the similarity to stored examplar; while the feature theory are classified based on sharing features that belong to category.

Some argues that categories are formed by means of associative learning where features of category become associated with thee category label. Blocking is a key characteristic of associative learning

=>Shanks (1990)- subjects were given trials where medical symptoms paired with disease diagnosis. They were provided with two diseases: one common while another rare, and three symptoms including one targeted symptom. Blocking is formed with lesser trials between rare disease and the targeted symptom.

Association between stimuli only forms if the category is surprising. A rare disease is more surprising in this case.

This suggests that associative learning is the best explanation of categorization task in humans.

Can animals form superordinate categories?

=>Wasserman, De Voider & Coppage (1992)- trained pigeons to make response A to category 1 and 2, and to make response B to category 3 and 4. Then, they were trained to make response C to category1 and response D to category 3. They were later tested with category 2 and 4, with choice of response C and D. They made response C to category 2 and response D to category 4.

They seem to treat category 1 and 2 as equivalent because of the earlier paring with response A in training phase,

Is this thw same as how human do it?

It is argued that this is not true categorization that seen in humans, but just simple associative learning.

Abstract concept formation in animals?

=>Wasserman, Hugart & Kirkpatrick-Steger (1995)- showed pigeons complex stimulus displays and given a choice of red or green key. The pigeons were rewarded for pecking the red key when a picture of same items are schown and green key for different items shown in a picture. They seems to be able to peck on the correct key when different arrays of a different specific icons.