WEEK 5 Flashcards
1
Q
top-down neuromodulation
A
- hitting higher parts of the brain, like the cortical layers
- repetitive transcranial magnetic stimulation (rTMS)
- transcranial direct current stimulation (tDCS)
- deep brain stimulation (DBS)
2
Q
bottom-up neuromodulation
A
- stimulating an external nerve to get a current back into the brain
- vagal nerve stimulation (VNS)
- trigeminal nerve stimulation (TNS)
3
Q
Faraday’s law of magnetic induction
A
- if we have a magnetic coil placed above the skull, by turning it off and on, the magnet will induce electrical current within the brain. this results in neurons firing as they’ve been depolarized.
4
Q
slow TMS
A
- 1 HZ every second, inhibits underlying neurons
5
Q
fast TMS
A
- 5 HZ about 10 times every second, stimulates underlying neurons
6
Q
key issues with the magnetic coil
A
- only affects the area directly under the coil’s sweetspot, which is incredibly large
- superficial penetrance (1 cm of the cortex)
- can be sited manually (less accurate) or computer guided (more accurate)
7
Q
rTMS: mechanism of action
A
1) though it immediately alters synaptic firing, the effects happen once TMS is taken away. therapeutic effects occur in long term changes to the brain, including LTP and LTD, important in memory formation and how neurons connect to each other over time.
2) affects cellular level changes through expression of various genes that code for neuronal plasticity.
8
Q
rTMS and depression
A
- based on the underactive model of depression, notably hypoactivity in the dorsolateral PFC and the limbic system.
- we apply fast rTMS to the left side of the dPFC to stimulate it.
- proven effective in depression, level A recommended (regarded as a definite antidepressant)
9
Q
rTMS and auditory hallucinations
A
- when people hallucinate, their speech network is overactive. we then apply slow TMS to inhibit it at the temporoparietal junction.
- overall it helps, with moderate but statistically significant effects
10
Q
tDCS
A
- application of a small direct current through the scalp to the brain. instead of a magnet, it’s an electrical current to affect the firing of brain cells.
- small current (1-2 mA), 2 electrodes coated in saline on the scalp.
- less studied
- doesn’t make neurons fire instantly, it just alters their susceptibility to inputs. when removed, the affected brain region will be more or less likely to fire.
11
Q
VNS
A
- stimulate peripheral cranial nerves to get the current to pass back up into the brain and hit regions we hope will be therapeutic
- activating the vagal nerve affects serotonin and noradrenalin pathways, both important in some people with depression.
- invasive technique that requires surgery to insert a lithium battery on the vagus nerve to stimulate it.
12
Q
VNS: ethical considerations
A
- most data on VNS come from studies with treatment resistant patients. we can’t know its effectiveness for sure, then.
- we can’t double-blind it. it’s unethical to operate on someone without providing them with treatment.
13
Q
TNS
A
- stimulate a cranial nerve, which conveys sensory info from the face to the brainstem, and get a current to go back to the brain.
- non-invasive
- 2-saline soaked electrodes are placed on the forehead
- studies have been in tx-resistant patients and methodologically weak
14
Q
DBS
A
- surgically implant two electrodes that will stimulate specific brain regions
- mostly for treatment resistant cohorts with severe symptoms
- stimulation is continuous
- best established in parkinson’s and essential tremor
- best data in tourette’s and OCD
- trialled for tx-resistent depression
15
Q
DBS: key issues
A
- batteries need to be replaced every few years through surgery
- possibility of serious side effects including death and neuropsychiatric illness
- ethical complications when double-blinding
- no consensus on how it works, really
16
Q
neuromodulation and acceptability
A
majority are against it, because:
- it looks and sounds like ECT
- the long-term side effects are unknown
- it adopts a mechanistic view of mental illness, one that is based on biological parameters and not the full story
17
Q
keefe and cognitive enhancement
A
“cognitive enhancement without a parallel intervention is like eating protein without exercising”
- neuromodulation might just prime the brain for further intervention
18
Q
3 psychological treatments for psychosis
A
1) CBTp for - positive symptoms
2) Family therapy - for relationships
3) Social Skills Training (SST) - for relationships
19
Q
Family therapy
A
- individuals who return to live with their parents are at higher risk of relapse because of heightened expressed emotion. family therapy aims to help families and patients understand the nature and symptoms of psychosis and to negotiate a new relationship
20
Q
SST
A
- individuals who leave the hospital and reintegrate into society lack social skills.
- SST teaches individuals how to recognise expressions, initiate convos, and make appropriate responses.
- evidence that it increases social skills, but doubts on its long term benefits
21
Q
CBTp
A
- works particularly well for people with chronic disorders
- reduces delusional conviction and relapse
22
Q
Schizophrenia: cognitive problems
A
- impairments in all cognitive domains, notably verbal memory, some problems with visual processing.
- at severe levels, people in an acute episode experience periods where they can’t communicate. in a non-acute state, patients are very aware of their cognitive difficulties.
- in the early stages, people notice changes in their cognition
23
Q
4 domains of cognition
A
1) executive function
2) long-term memory
3) working memory
4) attention
24
Q
early cognitive difficulties in psychosis
A
- developmental lag of about 6-18 months in those who went on to develop psychosis
- children who developed psychosis were even delayed at age 3
- at 16, they performed significantly worse on all cognitive domains
- 40% of children aged 7 had such severe difficulties they qualified for cognitive deficits (1 SD under the average)
25
cognition and the cost of care
- cognitive problems predict the cost of care, as they require more residential and inpatient services.
- the severity of cognitive difficulties predict cost of health and social care
26
Rethink: what people with psychosis want
1) a job
2) fulfilling social relationships
3) ability to look after themselves
4) independence
27
cognition and recovery programs
for work, social skills, independence, and life skills - cognition was a predictor of how beneficial the interventions were. people with low working memory did poorer on social skills. cognition predicted adherence to work rules. psychotic symptoms accounted for much less of the variance on outcome in independence programs compared to cognition.
28
5 learning principles (CR)
1) massed practice
- tasks are repeated
- difficulty gradually increases
- developing cognitive skills that become automatic
- learn broad principles that can be applied to a number of situations
2) errorless learning
- ensures individuals don't learn errors
- correct performance is clear
- keeps learning accurate, and reinforcement + motivation high
3) verbal monitoring
- remember task instructions by encouraging them to overtly and eventually internally verbalize them
4) scaffolding
- learning support so tasks are manageable but challenging
- learning support is gradually withdrawn so people learn to self-scaffold
5) using strategy
- teaching people how to improve task performance through the use of strategies
29
Cognitive Remediation Therapy (CRT)
- helps achieve functional recovery based goals rather than improving mood or symptoms
- teaches individuals to use their strengths to develop cognitive skills and strategies
- learning is personalized and motivation
- some evidence that it improves overall cognition, functioning, and symptoms, though the durable changes were on cognition and functioning.
- has a major effect in people who very low functioning, but little to no effect for those who were high functioning
30
metacognition
= thinking about thinking, knowledge and beliefs about your own thinking, ability to monitor and evaluate your thinking and tot control and regulate your cognitive and behavioral performance. metacognition has an effect on how cognitive improvements are used in daily life, so it also improves functioning.
31
2 types of metacognition
1) metacognitive knowledge
- knowledge about what affects your and others thinking, your strengths and difficulties, and the skills and strategies needed for different tasks.
2) metacognitive regulation
- ability to reflect on your thinking skills, and to plan, monitor, evaluate, and adjust them online.
32
metacognition and change
both types of metacognition help people to generalize from learning in therapy to applying the strategies in real life. they help people change behavior by helping people believe they can change.
1) set goals
2) target metacognition by teaching metacognitive knowledge and regulation
3) integrate into everyday life
33
ketamine
- works on glutamate signaling
- induces bizarre changes on consciousness which resemble psychosis
- biopertin and the lily compound LY-023 block its effect
- the most convincing drug model of schizophrenia, as it reproduces the majority of symptoms, including negative symptoms and cognitive detriments.
- blocks the NDMA channel which opens when glutamate binds to it.
34
NMDA channel
- opens when glutamate binds to the NMDAR.
- NMDAR is an essential component to learning and memory.
- when open, NMDA channels let in sodium and calcium, setting off a strengthening of the synapse.
- the more traffic through a synapse, the stronger is becomes (LTP)
- the NMDAR has two binding sites, one for glutamate and one for glycine. drugs that target the glutamate site can be very toxic, like ketamine.
35
bitopertin
antipsychotic that blocks the glycine transporter to stop it from being recycled back into cells. glycine will then be more available for binding to the NMDAR.
- benefits against the negative symptoms of schiz
36
LY-023
- blocks the effect of ketamine in animals and has been used in a human trial. it was found to be as effective as olanzapine without side effects.
- acts on autoreceptors
37
sodium nitroprusside (SNP)
- prevents the effect of ketamine in animals
- nitric oxide (NO) donor. NO is a natural signaling system in the body, and a neurotransmitter in the brain
- its administration led to marked and quick reductions in psychotic symptoms over several hours. a single injection could lead to maintained improvements in schizophrenia over the next month.
38
Nitric oxide
- produced at glutamate synapses
- gaseous neurotransmitter which diffuses in all directions after its production.
- can cause blood vessels to dilate - BOLD response
- glutamate synapses signal the need for blood born resources via release of NO
- first retrograde signal to be discovered
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