Cognitive models in psychosis Flashcards
What brain structures are dopaminergic neurons found in?
Mid brain structures
Substantia Nigra [SNc]
Ventral Tegmental area [VTA]
Where do the dopaminergic neuron axons, located in the SNc and VTA, project to?
The axons project to the
- striatum,
including the caudate nucleus, putamen,
- ventral striatum, or nucleus accumbens, shown with a red line and the green line.
The dorsal and ventral prefrontal cortex are also projected too, and you can see that here displayed with the blue lines.
What found in post-mortem studies of patients with schizophrenia suggests higher levels of dopamine?
higher receptive density of D2 receptors
What is the relationship between the sensitisation of the mesostriatal dopamine system and psychotic symptoms in schizophrenia?
The sensitisation of the mesostriatal dopamine system, which includes dopaminergic pathways in the brain, has been linked to the severity of psychotic symptoms in schizophrenia. This suggests that the more the dopamine system is dysregulated, the more severe the psychotic symptoms are likely to be.
What role does dopamine D2 receptor antagonism play in the treatment of schizophrenia?
Dopamine D2 receptor antagonism is fundamental in the treatment of schizophrenia as it has been shown to significantly improve psychotic symptoms. Antagonists block the D2 receptors, countering the effects of dopamine dysregulation that contribute to psychosis.
What evidence supports the link between striatal dopamine dysregulation and schizophrenia?
Robust evidence from molecular imaging studies indicates that dis-regulated striatal dopamine is implicated in schizophrenia. These studies show that alterations in the function of the striatal dopamine system are associated with the presentation and severity of psychotic symptoms.
What has PET imaging revealed about L-DOPA uptake in patients with schizophrenia compared to controls?
PET imaging studies have demonstrated that L-DOPA, a precursor to dopamine, is taken up more rapidly in patients with schizophrenia than in control subjects. This finding supports the hypothesis that patients with schizophrenia may produce more dopamine.
What are the different neurotransmitter pathways that are thought to impact the negative and positive symptoms found in schizophrenia and what are the aims of the treatment in each case?
what are the 4 dopamine pathways?
Mesolimbic Pathway:
Mesocortical Pathway:
Nigrostriatal Pathway:
Tuberoinfundibular Pathway:
Give an overview of the Mesolimbic Pathway:
Originates from the ventral tegmental area (VTA).
Projects to various limbic structures, including the nucleus accumbens, part of the ventral striatum.
Often associated with the reward system of the brain, pleasure, and reinforcement; dysregulation in this pathway is implicated in the positive symptoms of schizophrenia and in addiction.
Give an overview of the Mesocortical Pathway:
Also originates from the VTA.
Projects to the prefrontal cortex, including the dorsolateral prefrontal cortex.
Involvement in cognitive control, motivation, emotional response; dysfunctions in this pathway are associated with the negative and cognitive symptoms of schizophrenia, such as blunted affect and impaired executive function.
Give an overview of the Nigrostriatal Pathway:
Originates from the substantia nigra, specifically the pars compacta region.
Projects to the striatum, which includes the caudate nucleus and putamen.
Plays a crucial role in the coordination of movement; degeneration of this pathway is a hallmark of Parkinson’s disease.
Give an overview of the Tuberoinfundibular Pathway:
Originates from the hypothalamus.
Projects to the pituitary gland.
Regulates the release of prolactin by inhibiting its secretion; antipsychotic drugs, which block dopamine, can disrupt this pathway and lead to elevated prolactin levels, resulting in side effects such as galactorrhea and amenorrhea.
What was the main observation in the response of dopamine neurons when monkeys received an unexpected weak liquid reward?
[study by Schultz and colleagues on dopamine release in response to stimuli and rewards in monkeys.]
The main observation was an increase in firing of dopamine neurons at the same time as the unexpected reward was given, indicating a surprise or salient event. This response to unpredicted primary rewards varies directly with the reward magnitude.
How does the dopamine response change during the course of learning when a reward is given as expected after a conditioned stimulus?
[study by Schultz and colleagues on dopamine release in response to stimuli and rewards in monkeys.]
During the course of learning, the dopamine response to the reward gradually decreases and a response to the conditioned stimulus that predicts the reward develops. The dopamine signal shifts from the reward to the predictor stimulus.
What happens to dopamine release when a conditioned stimulus is presented and the expected reward follows?
[study by Schultz and colleagues on dopamine release in response to stimuli and rewards in monkeys.]
There is a slight peak of dopamine release following the stimulus, reflecting the recognition that a reward is to come. However, when the expected reward is given, there’s no significant increase in dopamine release since there is no prediction error; the event occurred as expected.
Describe the dopamine response when a reward is predicted after a conditioned stimulus but is not given.
[study by Schultz and colleagues on dopamine release in response to stimuli and rewards in monkeys.]
Initially, there is a spike in dopamine release upon the recognition of the conditioned stimulus, but if the predicted reward does not follow, dopamine release decreases below normal levels, reflecting a negative prediction error.
What is the key message about the role of surprise in dopamine-mediated learning from Schultz’s study?
The key message is that the mismatch between what is expected and what actually occurs (surprise) drives learning. Dopamine release increases when events are better than expected, and there is a negative prediction error when events are worse than expected.
According to Miller’s hypothesis, how might an excessive supply of cerebral dopamine contribute to the positive symptoms of schizophrenia?
Miller proposed that in schizophrenic patients, an excessive supply of dopamine may facilitate the acquisition of associations between unrelated units of information, leading them to be treated as meaningful combinations. This can result in the formation of delusions and is associated with the positive symptoms of schizophrenia.
In the context of Miller’s hypothesis, how can aberrant salience lead to the formation of delusions in schizophrenia?
Aberrant salience occurs when a non-meaningful stimulus evokes dopamine firing, making it overly salient and attention-grabbing. This can lead individuals to form connections and seek explanations for these salient experiences, often resulting in the development of delusions.
What is a ‘delusion of reference’ as explained by Miller’s hypothesis, and how might it manifest in a patient’s experience?
A delusion of reference is an inference that a specific and unrelated stimulus is directly related to oneself. For instance, a patient might believe messages on TV are intended for them, assigning excessive salience to these messages and interpreting them as personally significant.
According to Miller’s hypothesis, how might antipsychotics affect the process of aberrant salience and its associated distress in schizophrenia?
Antipsychotics can block the aberrant salience of stimuli, supporting the extinction and unlearning of the associations that lead to delusions. However, they may also reduce the salience of normal events, potentially affecting motivation and normal emotional responses.
What is reinforcement-related speeding?
attributed to the anticipation of a potential reward on such trials leading to enhanced motivation and hence faster responding.
Faster reaction times in response to rewarding stimuli than neutral stimuli
In the reaction time study with psychosis and controls, with a reward and neutral type task, what difference was found? MURRAY
the difference was patients were significantly faster than controls on neutral trials.
In the Murray 2008 study, more positive symptoms were associated with a __________ distinction between ________ and non-__________ events in the brain
What is Anhedonia?
What is avolition?
What symptoms can in fact worsen with antipsychotics?
Anhedonia and Avolition
What did researchers start to hypothesise when studies showed that patients showed liking and enjoying positive things, just as much as non clinical patients, when the thinking had previously been that they do not experience pleasure?
That measures used to assess anhedonia may not reflect cons ummatory (in the moment) pleasure, but rather focus on the ability to anticipate pleasure. even thought you might like chocolate, you might not have the drive to go to the shop and buy it.
What tasks are used to investigate reward anticipation?
Neuroimaging studies in patients with schizophrenia support abnormalities in processes related to the anticipation of…..
reward
Unmedicated patients showed reduced_________ activation during the presentation of reward-indicating cues which is inversely correlated with the severity of ___________.
higher symptoms - lower activation in this area.
What does this suggest? [studies related to anticipation of reward]
That atypical medication might normalise the reward response or that the medication is given to patient groups that are fundamentally different. [but not gender, age etc]
What brain areas are implicated in these processes?
dorsal later PFC
orbital FC
anterior cingulate cortex
Evidence from the the wisconsin card sorting task has shown that people with schiz. may have problems……
tasks where feedback changes quickly. they learn 1st category well, but then have problems switching. explicit feedback not integrated. difficult to update value representations.
What was the outcome of this study
people with more negative symptoms were less likely to make more effort when the reward was certain. they may have computed the effort wasn’t worth it, when it was most salient.
According to ICD 10 how does psychosis present and what are some of the abnormalities of behaviour?
What percentage of patients with schizophrenia will experience auditory hallucinations?
25% of people who experience auditory hallucinations have done what?
Attempted suicide in response to these voices
What percentage of patients remain refractory to treatment for auditory hallucinations?
25-30%
What two areas of the brain seem to be active when people are hearing voices/hallucinations according to the Shergill, Brammer 2000 study?
Both speech and hearing areas.
Broca’s area and inferior frontal gyrus
According to Shergill 2001 with health control people, what did they see in the brain fMRI, when people were asked to generate words in their mind, with no sound or movement?
similar pattern of activation to people with auditory hallucinations.
What is the superior temporal gyrus responsible for?
monitoring of your own speech + auditory processing
What is the cerebellum responsible for?
monitoring motor movements
What is the parahippocampal gyrus responsible for?
In this study showing the difference in active brain regions between health controls and patients prone to auditory hallucinations, what areas were less active in people with schizophrenia?
What did this 2010 study show about the difference between healthy controls and patients prone to auditory hallucinations related to listening to external speech?
In both groups, when the speech was external, the left superior temporal gyrus was activated, and when they were prompted to listen to inner speech, in the health ppl, they flicked an internal switch that turned down the hearing part of the brain, but in patients with schizophrenia this signal was really weak and they only partially turned down the hearing part of the brain and so it mostly stayed in the external hearing part.
What area does the superior longitudinal fasciculus tend to link to?
The frontal to the temporal cortex
What brain regions are these three?
What was shown about the integrity of white matter bundles between brocas’ Superior longitudinal fasiculus and the speech perception area between people who are currently hallucinating and people that have never hallucinated??
What’s the difference between moving the lever with your own finger and moving the lever with a joy stick, in the experiment where you need to match the pressure from the otherside with your other hand?
You will have to apply more force when you do it with your hand, and less effort when you do it with the jobstick.
with the jot stick you’re not using so much corollary discharge.
When moving the lever directly with their finger, there’s a greater involvement of corollary discharge. This is because the brain is actively processing and anticipating the sensory feedback from the direct physical interaction. The brain predicts the consequences of the self-initiated movement, which affects the perception of effort and force required.
On the other hand, when using a joystick, the direct physical connection is removed. The sensory feedback and motor action are less directly linked, leading to a reduced role of corollary discharge. Since the brain is not anticipating and adjusting for the sensory feedback of the movement to the same extent, the perceived effort and actual force applied may be lower.
Does attenuation of the signal in the sensory cortex have a temporal element?
yes it only attenuates within a particular time window. so if there is a delay, there is less attenuation in the sensory cortex .
What was negatively correlated with PANSS hallucinations score in a corollary discharge experiment?
Movement-related sensory attenuation
What is the difference between health people and schizophrenic people and their somatosensory cortex attenuation?
Give a top level explanation of what TMS is.
Transcranial Magnetic Stimulation is a safe, non-invasive technique for stimulating or inhibiting cortex.
an alternating magnetic field in a coil induces a weak electric current in the underlying cortex.
What’s the difference between hot and cold cognitive mental processes?
What are some examples of double dissociations found in real life?
What are the key social cognitive domains?
What is Theory of Mind?
What is emotion perception?
Explain social perception and tests for it…
Explain social knowledge and what other cognitive domain it interfaces with
What is attribution style?
How do we measure attribution
Which allows for distinction between
- external personal attributions / caused by others
- external situational attributions / caused by the situation
-internal attributions / caused by oneself
What is an example of two brain regions associated with social processes that are not entirely separate and what are they involved in?
What brain regions, implicated in emotional recognition processes are involved in face perception?
What brain regions, implicated in emotional recognition processes are involved in voice perception?
What brain regions, implicated in emotional recognition processes are involved in emotion experience?
What brain regions, implicated in emotional recognition processes are involved in emotional regulation?
What brain regions, implicated in emotional recognition processes are involved in mentalising, theory of mind?
The brain areas typically activated during social-cognitive processing overlap with brain regions of the……..
What 2 impairments with alrge effect sizes did a meta analysis looking at schizophrenia and theory of mind find
What is the link between schizophrenia symptoms and attribution style?
Research supports a pattern of lower brain activation in schizophrenia patients in areas including…
What are the areas of higher brain activation in schizophrenia patients and what could it point to?
