Learning about the world

Question 1

What is the main neurotransmitter involved in reward learning (reward-motivated behaviour)?

Answer 1

Dopamine

Question 2

What characterises the dopamine activity in a schizophrenic person?

Answer 2

Aberrant dopamine activity

• higher D2 receptor density -> higher levels of dopamine
• L-Dopa taken up quicker -> higher production of dopamine

Question 3

What have molecular imaging suites shown on the association between dopamine activity and psychotic symptoms?

Answer 3

Degree of sensitisation of mesostriatal dopamine system is associated to severity of psychotic symptoms

• > amphetamines and cocaine increase dopamine and worsen symptoms in schizophrenic patients
• > D2 receptor antagonists improve psychotic symptoms

Question 4

To which neurotransmitter pathway are the negative symptoms of psychosis associated?

Answer 4

Mesocortical pathway

Question 5

To which neurotransmitter pathway are the positive symptoms of psychosis associated?

Answer 5

Mesolimbic

Question 6

What is the aim of the treatment of negative symptoms in schizophrenia?

Answer 6

Increase dopamine neurotransmission

Question 7

What is the aim of the treatment of positive symptoms in schizophrenia?

Answer 7

Slow down dopamine neurotransmission

Question 8

What are prediction errors?

Answer 8

Dopamine-dependent signal that play a role in learning

• mesolimbic dopaminergic regions

Question 9

What is the dopaminergic response when there is no prediction of a reward and a reward occurs (Schultz, 1971)?

Answer 9

• Surprise = salient event -> increase in firing when reward is given
• Response variation to unpredicted primary rewards
• > the nice the reward, the higher the signal

Question 10

What is the dopaminergic response when a reward is predicted and a reward occurs (Schultz, 1971)?

Answer 10

• Dopamine increase at presentation of conditioned stimulus
  = recognition that reward will come
• Dopamine signal shifts in time from reward to predictive stimulus = prediction learning
• When reward given as expected, there’s no increase in dopamine release
• > no prediction error

Question 11

What is the dopaminergic response when a reward is predicted but no reward is given (Schultz, 1971)?

Answer 11

Dopamine release decreases to below normal levels

Question 12

What is the reward prediction learning effect in the study of Schultz (1967)?

Answer 12

Dopamine signal shifts in time from reward to prediction stimulus

Question 13

What is the effect of expectation and learning on dopamine release?

Answer 13

As learning occurs, dopamine firing adjusts

• when subject geins to expect certain outcome from certain scenario, prediction error becomes smaller and smaller

Question 14

What is the consequence of the aberrant dopamine activity in schizophrenic patients as explained by Kapur (2003, 2004)?

Answer 14

Aberrant salience and positive symptoms

1. Dysregulated firing and/or release of dopamine
2. Aberrant sense of novelty and abnormal assignment of salience to stimulant internal representations
   - > stimulus that may not be meaningful evokes dopamine firing
3. Delusions as negative cognitive schema the patient develops to explain aberrant salience
   - > an inference is required to account for salient/odd experiences that will be interpreted in meaningful way (e.g. sense of persecution)

-> they shape perception and interpretation of new information

Question 15

When are psychotic patients treated according to Kapur (2003, 2004)?

Answer 15

When the aberrant salience assigned to stimuli and internal representations impacts on behaviour or causes distress

Question 16

What is the effect of antipsychotics according to Kapur (2003, 2004)?

Answer 16

• Block effects of dopamine and dampen the salience of preoccupying symptoms
• May also dampen the motivational salience of normal events

Question 17

What are the reward-related areas of the brain?

Answer 17

• Mesocortical pathway
• Mesolimbic pathway
• Nigrostriatal pathway
• Prefrontal cortex
• Nucleus accumbens
• Striatum
• Ventral tegmental area
• Substantia nigra

Question 18

What did the study of Murray and colleagues (2008) on salience and (first episode) psychosis show?

Answer 18

• Instrumental learning task involving monetary gains to increase motivation
• Patients and controls learned to choose the high probability stimulus on reward trials (no significant differences)
• Reinforcement-related speeding: both patients and controls were significantly faster on reward trials than neutral trials
• BUT, patients were significantly faster than controls on neutral trials
• > psychotic patients found the neutral trials inappropriately motivationally significant
• More positive symptoms were associated with lower distinction between salient and non-salient events in the brain (observed in substantia nigra and VTA)

Question 19

Which model of psychosis does the study of Murray and colleagues (2008) support?

Answer 19

Model of psychosis that postulated abnormal dopamine-dependent motivational salience as key mechanism of symptoms

Question 20

Which cause was attributed to the reinforcement-related speeding observed in the study of Murray and colleagues (2008)?

Answer 20

Anticipation of potential reward on reward trials

• > enhanced motivation
• > faster responding

Question 21

What did the study of Corlett and colleagues (2007) show?

Answer 21

• Brain activation in controls was greater for salient than for non-salient events (as in Murray’s study)
• effect attenuated and/or partially reversed in patients
• Higher delusions were associated with the brain response only in prefrontal regions, not midbrain

Question 22

How can learning occur in psychotic patients if their brain system is not functioning normally (Murray, Corlett and Fletcher, 2010)?

Answer 22

• Standard brain activation patterns may be present in psychosis but partially obscured by grater noise
• Brain signals may be more sensitive to real group differences than behavioural measures
• Patients may achieve comparable levels of performance to control subjects by employing alternative or compensatory neural strategies outside areas of interest
• Could be due to nature of task -> differences may become visible once task demands increase

Question 23

What is anhedonia?

Answer 23

‘Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day’

Question 24

What is avolition?

Answer 24

“Poverty of will” and disabling restriction in the initiation of activity, including goal-directed behaviour

Question 25

What are the suggested to key negative symptoms in schizophrenia?

Answer 25

• Anhedonia

- Avolition

Question 26

What characterises negative symptoms in schizophrenia?

Answer 26

• Associated with reduced real-world functioning
• Poorly understood
• May worsen under antipsychotic treatment
• Hypothesis on aetiology: hypodopaminergic state specifically in prefrontal areas
• Research supports role of striatal reward mechanisms

Question 27

What does the large body of behavioural research suggest on the capacity of patients with schizophrenia to experience pleasure?

Answer 27

Intact “hedonic experience”

• majority of studies show people with schizophrenia liking or enjoying positive things

Question 28

What is the hypothesis of researchers that showed people with schizophrenia have an intact “hedonic experience”?

Answer 28

Clinical measures used to assess anhedonia may not reflect consummatory (in the moment) pleasure BUT rather focus on ability to anticipate pleasure

• may explain why normal experiences of pleasure do not translate to motivational (goal-directed behaviour)
• > potential lack of anticipation of enjoyable effect of stimuli in schizophrenia

Question 29

Which tasks investigate reward anticipation?

Answer 29

• Learning task used by Graham Murray and colleagues (2008)

- Monetary incentive delay task

Question 30

What did the monetary incentive delay task used by Jackal and colleagues (2006) show?

Answer 30

Visual cues predicted that a rapid response to a subsequent target stimulus would result either in monetary gain or loss, or would have no consequence

Question 31

What do neuroimaging studies show on reward anticipation in patients with schizophrenia patients?

Answer 31

Abnormalities in processes related to anticipation of reward

• reduced ventral striatal activation during presentation of reward-indicating cues
• > inversely correlated with severity of negative symptoms
• similar patterns of reduced activation in ventral striatum in patients on typical mediation, but no atypical medication

Question 32

What could explain why patterns of reduced activation in the ventral striatum are observed in schizophrenic patients on typical medication but not atypical medication?

Answer 32

• Atypical antipsychotics may normalise the reward response

- Or medication given to patients groups are fundamentally different

Question 33

What does value computation in anticipatory pleasure refer to?

Answer 33

Value of reward or desirable outcome

• how much effort or “work” it will take to get that reward or outcome

Question 34

Why is it important to integrate value computations alongside anticipatory pleasure?

Answer 34

Drives the ability to generate and execute action plans necessary to achieve valued outcomes

Question 35

Which brain areas are implicated in the integration of value computations to anticipatory pleasure?

Answer 35

Frontal brain areas closely linked to striatal regions

• dorsolateral prefrontal cortex
• orbitofrontal cortex
• anterior cingulate cortex

Question 36

What does the research evidence suggest on the reward value in schizophrenia (Bring and Barch, 2014?

Answer 36

Impairments in generating, maintaining and updating mental representations of value
- partly due to other cognitive problems (memory)

Aberrant value-effort computations: less effort for guaranteed monetary rewards in patients with negative symptoms vs controls