Background and aim
Dopamine
A neurotransmitter involved in movement, motivation and processing information; unusual levels of activity are linked to several conditions.
- People with schizophrenia show under-activity of the prefrontal cortex, the part of the brain used for planning, reasoning and switching strategy.
- On the dopamine hypothesis, dopamine activity is what drives that prefrontal work, so weak prefrontal activity should go with weak dopamine signalling there.
- If that is right, a drug that stimulates dopamine ought to raise prefrontal activity and improve scores on a task the prefrontal cortex is needed for.
- Amphetamine is one such drug, because it increases the amount of dopamine acting at the synapse.
- Aim: to investigate activity in the prefrontal cortices of people with schizophrenia.
- Giving amphetamine raised dopamine activity, and prefrontal activity went up while card sorting scores improved.
- That rise happened even though overall blood flow in the brain fell, so the effect was specific to the prefrontal region under cognitive demand.
- The study is used as support for the dopamine hypothesis, because it ties dopamine activity to how well the brain performs a thinking task.
Method
Placebo
A dummy treatment that contains no active drug, given so that a participant does not know whether they have had the real drug and the drug's effect can be compared fairly.
- Design: a laboratory experiment using repeated measures, so each participant was tested with and without amphetamine on two different days.
- Counterbalanced: half the participants took amphetamine on the first day and half took the placebo first, which cancels out order effects such as practice on the task.
- The placebo meant participants did not know which they had been given, so their own expectations could not shape their scores.
- Sample: ten in-patients from mental health research wards in the USA.
- Controls: every participant's symptoms had already been stabilised with medication before testing began.
- None of them was physically ill, and none was using alcohol or other drugs.
- Repeated measures means the same ten people produced both sets of scores, so the comparison is within a person rather than between two groups.
- Every participant was already on medication, which is a control here and a limitation later, because that medication was also acting on dopamine.
Variables and apparatus
- Independent variable: whether participants were given a placebo or 0.25 mg/kg of oral dextroamphetamine.
- Dependent variable: performance on a cognitive task, the Wisconsin Card Sort Test, which needs the prefrontal cortex to plan and to switch strategy.
- In that test a person sorts cards by a rule they are never told, and the rule changes without warning, so they have to notice the change and switch.
- Apparatus: brain activity was measured by a SPECT (single-photon emission computed tomography) scan, which tracks regional cerebral blood flow as a sign of how hard an area is working.
- Participants also performed a sensori-motor control task alongside the cognitive task, so any change could be tied to the cognitive demand rather than to general arousal.
- Dopaminergic neurons release dopamine into the synapse, and amphetamine increases how much dopamine acts there.
- More dopamine at the synapse means more signal reaching the next neuron in the prefrontal cortex.
Results
- There was a significant difference between the amphetamine and placebo conditions on the cognitive task, but not on the sensori-motor task.
- Amphetamine significantly increased prefrontal cortex activity during the cognitive task, and task scores were higher.
- That rise happened despite the drug reducing overall blood flow in the brain, so the effect was specific to the prefrontal region under cognitive demand.
Conclusions
- Dopamine modulates and enhances cortical activity, since amphetamine stimulates dopamine activity and prefrontal activity went up.
- The prefrontal under-activity seen in schizophrenia is therefore at least partly reversible by dopaminergic means.
- Link to the theory: this supports the dopamine hypothesis, the biological explanation of schizophrenia, in which dopamine activity at the synapse shapes how the brain functions.
- This is a laboratory experiment rather than a natural experiment, because the researchers decided who got the drug and who got the placebo.
- Blood flow did not rise everywhere, because overall blood flow fell while prefrontal activity during the cognitive task rose.
Criticisms
- Strength, the design: repeated measures removes individual differences, counterbalancing cancels order effects, and the placebo blinds the participant.
- Strength, the data: scan readings and task scores are objective and quantitative, so another team could repeat the study and check the figures.
- Strength, the control task: the sensori-motor task pins the effect to the cognitive demand rather than to general arousal from the drug.
- Sample: ten in-patients is too small to represent everyone diagnosed with schizophrenia.
- Validity: sorting cards to a hidden rule is too artificial to say much about everyday thinking.
- Extraneous variable: the medication that stabilised symptoms was itself altering dopamine activity, so its effect cannot be separated from the amphetamine's.
- Dated findings: schizophrenia is diagnosed differently now, so these ten patients may not match who would be diagnosed today.
- Ethics: using scanning equipment for research alone carries risk, and so does giving amphetamine to people who are already unwell.
- Nature and nurture: the biological explanation sits on the nature side of this debate, because it explains schizophrenia through dopamine and brain function.
- That leaves out nurture, such as upbringing, stressful life events and rejection by other people.
- Amphetamine is used here as a research tool rather than as a treatment, since raising dopamine can also make positive symptoms worse.
- One study cannot carry the dopamine hypothesis on its own, so it sits alongside the evidence from anti-psychotic drugs.
Turning this into marks
- When two criticisms are asked for, make them genuinely separate rather than one criticism rephrased.
- Name the SPECT scan and the Wisconsin Card Sort Test, because a general reference to a brain scanning study does not secure the knowledge mark.
- The mark most often lost is reporting the rise in prefrontal activity without saying that overall blood flow fell.
- State the aim of Daniel et al. (1991).
- Why is this a laboratory experiment rather than a natural experiment?
- What happened to prefrontal activity, and what happened to overall blood flow?
- Why was a sensori-motor control task included?
- How does the study support the dopamine hypothesis?