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Psychology & Neuroscience of Psychosis > Neuromodulation in psychosis > Flashcards

Neuromodulation in psychosis Flashcards

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1
Q

Which neuromodulation techniques are top down?

A
  • Repetitive transcranial magnetic stimulation (rTMS)
  • Transcranial direct current stimulation (tDCS)
  • Deep brain stimulation (DBS)
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2
Q

Which neuromodulation techniques are bottom up?

A
  • Vagal nerve stimulation (VNS)

- Trigeminal nerve stimulation (TNS)

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3
Q

Which neuromodulation techniques are non-invasive?

A
  • Repetitive transcranial magnetic stimulation (rTMS)

- Transcranial direct current stimulation (tDCS)

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4
Q

Which neuromodulation techniques are invasive?

A
  • Deep brain stimulation (DBS)
  • Vagal nerve stimulation (VNS)
  • Trigeminal nerve stimulation (TNS)
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5
Q

What characterises non-invasive neuromodulation techniques?

A

They are applied outside of the body

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6
Q

What characterises invasive neuromodulation techniques?

A

They require surgery: cutting through skin and bone

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7
Q

When was transcranial magnetic stimulation (TMS) developed?

A

1980s

- first new-wave neuromodulation technique

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8
Q

What is the basis of transcranial magnetic stimulation (TMS)?

A

Faraday’s law of electromagnetic induction

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9
Q

What are the two major ways of giving transcranial magnetic stimulation (TMS) and rTMS?

A
  • Slow rTMS (< 1Hz)

- Fast rTMS (> 5Hz)

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10
Q

What is the mechanism of action of slow rTMS?

A
  • <1Hz
  • Inhibit underlying neurons
  • causes depolarisation, and after in its absence it causes an inhabited pattern in neurons (they’re less likely to fire) for a period
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11
Q

What is the mechanism of action of fast rTMS?

A
  • > 5Hz
  • stimulatory to underlying neurons
  • causes the targeted area to be more likely to fire
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12
Q

How does transcranial magnetic stimulation (TMS) and rTMS work?

A

Magnetic coil turns on and off

  • induces electrical current within the bain (which works on electrochemical basis)
  • > firing - depolarisation of neurons
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13
Q

What are the key issues of the magnetic coil in TMS and rTMS?

A
  • Effects neurons directly under the coil ‘sweet spot’: 0.5cm diameter
  • > large part of the brain
  • Superficial penetrance (top 1cm of cortex)
  • Can be sited manually (less accurate) or computer guided (more accurate)
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14
Q

What is the mechanism of action of rTMS?

A

Alters synaptic firing immediately

  • slow or fast: involves processes including long-term potentiation (LTP) and long-term depression (LTD)
  • > memory formation and neuronal connectivity
  • When taken away, rTMS affect how regions connect and the changes in neuronal plasticity at cellular level
  • Therapeutic effects occur in long-term changes to the brain
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15
Q

What is the most studied paradigm with repeated transcranial magnetic stimulation (rTMS)?

A

Depression

- characterised by underactivation of certain parts of the brain

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16
Q

What is the neurophysiological principle characterised in the underactivation model of depression?

A

Hypoactive dorsolateral PFC and connected deeper limbic areas (striatum, thalamus, anterior cingulate cortex)

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17
Q

How is repeated transcranial magnetic stimulation (rTMS) used for depression?

A

Fast rTMS
- stimulatory -> enhances the functions

  • targets left side of dorsolateral PFC
  • limbic system out of reach with this tool
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18
Q

What explains the choice of the current typical paradigm of rTMS for depression?

A

Optimal parameters are still unknown

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19
Q

What is the effectiveness of rTMS for depression?

A
  • rTMS effective in depression
  • recent European expert consensus statement graded it “level A recommended”
  • > definite antidepressant effect
  • NICE updated guidance in December 2015 to note “adequate” efficacy
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20
Q

How is rTMS used for psychosis?

A

Commonly, to treat auditory verbal hallucinations

21
Q

How is rTMS used for auditory verbal hallucinations?

A

Neurophysiological principle of overactive speech network

  • > slow rTMS applied to temporoparietal junction (left or right)
  • > inhibits this network
22
Q

What explains the choice of parameters in a typical paradigm of rTMS for auditory verbal hallucinations?

A

Data are missing to inform on what the optimal parameters would be

23
Q

What is the effectiveness of rTMS for auditory verbal hallucinations?

A

Recent meta-analysis demonstrate a weighted effect size of 0.44

-> modest but statistically significant effect

24
Q

For which interventions has rTMS shown therapeutic promise?

A
  • Depression
  • Auditory verbal hallucinations in psychosis
  • Anorexia
  • Bulimia nervosa
  • Substance misuse
  • Gambling disorders
  • > re-regulating dysfunctional frontotemporal-limbic impulse control
25
Q

Can we regulate the cognitive control of emotion through neuromodulation?

A

Possibly, but current data still quite limited

26
Q

What is the mechanism of action of transcranial direct current stimulation (tDCS)?

A
  • Application of small direct current through scalp to the brain
  • > firing of brain cells
  • > modifies long-term neuronal potentiation, changing responses to subsequent inputs, by making neurons more susceptible
  • When taken away, the affected brain region will be more or less likely to fire afterwards
27
Q

What characterises the protocols of transcranial direct current stimulation (tDCS)?

A

Protocols less well-established than rTMS
- less spaciously focused

  • typically 20 minus continuous application
  • frequency of sessions vary
28
Q

Which major areas have been explored with transcranial direct current stimulation (tDCS)?

A
  • Depression
  • Hearing voices
  • Cognition
29
Q

Which neurophysiological principle is targeted with transcranial direct current stimulation (tDCS)?

A

Underachieve PFC

-> tDCS tries to enhance brain plasticity

30
Q

What is the effectiveness of transcranial direct current stimulation (tDCS)?

A
  • 2 meta-analyses with conflicting results
  • some emerging positive data on reducing auditory verbal hallucinations in psychosis
  • There’s interest in enhancing cognition following cerebrovascular accidents and in negative symptoms of psychosis
  • > Lots of variability between studies
31
Q

What is the principle of vagal nerve stimulation (VNS)?

A

Stimulate peripheral cranial nerves

-> get the current to pass back into the brain and hit regions

32
Q

What is the mechanism of the vagal nerve stimulation (VNS)?

A
  • Activation of peripheral cranial nerves alters firing rate of noradrenergic neurons in locus cureless and serotoninergic neurons in dorsal raphe nuclei
  • Activating vagal nerve can affect serotonin and noradrenalin -> depression
33
Q

How is vagal nerve stimulation applied?

A

Lithium battery generator is surgically inserted

  • stimulation applied on and off, targeting vagus nerve
34
Q

What are the key issues with the research on vagal nerve stimulation (VNS)?

A
  • Data collected on VNS based on cohorts significantly refractory to other treatments
  • > does it reflect the effectiveness of VNS?
  • Double-blind RCTs is ethically problematic for surgeons that would operate on people without giving active intervention to some
  • The current only single double-blinded RCT shows no improvements in VNS
35
Q

What is the principle of trigeminal nerve stimulation (TNS)?

A
  • Stimulation of external nerve

- Get a current to go back into the brain to change brain functioning (similar to VNS)

36
Q

What is the trigeminal nerve?

A

Cranial nerve that comes directly from the brain

  • conveys sensory information from the face to the brainstem
  • > Stimulation has been shown to change how cortex works
37
Q

What make trigeminal nerve stimulation (TNS) non-invasive?

A

It stimulates the nerve externally

  • 2 saline-soaked electrodes are placed on the forehead
38
Q

What are the key issues of trigeminal nerve stimulation (TNS)?

A
  • Most data are ‘open label’: trials of people who are treatment resistant due to refractory depression
  • Most people get the active intervention
  • Data are available to support efficacy BUT methodologically weak
39
Q

What is the current use of deep brain stimulation (DBS)?

A
  • Stimulation usually continuous and can be externally altered
  • Best established in Parkinson’s disease and essential tremor
  • Best data on Tourette’s syndrome and OCD
  • Has been trialed for treatment-refractory depression - all ‘open label’
  • BROADEN study to have RCT in depression (no progression to date)
40
Q

What makes deep brain stimulation (DBS) an invasive technique?

A
  • Brain surgery is needed (reversible)
  • Neurosurgical implantation, under general anaesthetic, of 2 electrodes that will stimulate very specific brain regions
  • Stimulators are implanted subclavicularly
41
Q

What are the key issues with deep brain stimulation (DBS)?

A
  • Batteries need surgical replacement every few years
  • Possibility of serious side-effects (including death) and can cause neuropsychiatric illness
  • Ethical complications four double-blind RCT where brain surgery is needed but intervention might not be given
  • No consensus on where and how often to taret certain parts of brain
42
Q

Which brain areas are considered in deep brain stimulation (DBS)?

A
  • Subgenual cingulate cortex
  • Rostral cingulate cortex
  • Inferior thalamic peduncle
  • Ventral striatum / nucleus accumbens
  • Lateral habenula
43
Q

What are the research difficulties in the treatment protocols of neuromodulation techniques?

A
  • All modalities have enormous variability
  • Overall, little consistency
  • Physiological characteristics of patient
  • Method for siting modality
  • Number of sessions, interval between sessions
  • Duration of sessions
  • Stimulation during session
44
Q

What explains the consistency between different protocols of neurmodulation techniques?

A

Studies are based on earlier research undertaken

-> no real biological rationale

45
Q

What is the main question regarding the challenge of diagnostic criteria and use of neuromodulation?

A

When and for whom might it work with neuromodulation?

Drysdale (2017):
- 4 neuroimaged biotypes in people with depression

  • Some of these biotypes were more responsive to TMS than others
46
Q

What is the issue with the mechanisms of neuromodulation?

A

Most treatments based on rather simplistic stimulation or inhibition paradigm

BUT brain is complex, with huge areas and vast networks of connections

  • > inhibiting one area, activates another area at the opposite side of the brain
  • > Neuromodulation has unknown effect at cellular level
47
Q

How acceptable is neuromodulation to patients?

A
  • Neuromodulation seen as something very mechanistic that focuses on biological changes in te brain rather than on external aspects of individual’s life
  • It is still kept inside research labs rather than being spread out onto clinics
  • Mixed results from patients and staff with general tendency against neuromodulation techniques
48
Q

What is the cost and access of neurmodulation?

A
  • Generally speaking, it would not be available to the public in the UK
  • More common in the US
  • Cost of TMS machine > 10,000£
  • Cost of tDCS machine < £1000
49
Q

What is the main factor in the cost of neuromodulation?

A

Clinician time:
- rTMS protocol might involve daily treatment, taking up to an hour per person, everyday for 2 weeks

  • Surgical techniques: 20,000 - 200,000£ per individual (depending on country)
  • > High cost must be counterbalanced against the cost of untreated illness

Psychology & Neuroscience of Psychosis (16 decks)

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