Neuromodulation in psychosis Flashcards
Which neuromodulation techniques are top down?
- Repetitive transcranial magnetic stimulation (rTMS)
- Transcranial direct current stimulation (tDCS)
- Deep brain stimulation (DBS)
Which neuromodulation techniques are bottom up?
- Vagal nerve stimulation (VNS)
- Trigeminal nerve stimulation (TNS)
Which neuromodulation techniques are non-invasive?
- Repetitive transcranial magnetic stimulation (rTMS)
- Transcranial direct current stimulation (tDCS)
Which neuromodulation techniques are invasive?
- Deep brain stimulation (DBS)
- Vagal nerve stimulation (VNS)
- Trigeminal nerve stimulation (TNS)
What characterises non-invasive neuromodulation techniques?
They are applied outside of the body
What characterises invasive neuromodulation techniques?
They require surgery: cutting through skin and bone
When was transcranial magnetic stimulation (TMS) developed?
1980s
- first new-wave neuromodulation technique
What is the basis of transcranial magnetic stimulation (TMS)?
Faraday’s law of electromagnetic induction
What are the two major ways of giving transcranial magnetic stimulation (TMS) and rTMS?
- Slow rTMS (< 1Hz)
- Fast rTMS (> 5Hz)
What is the mechanism of action of slow rTMS?
- <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
What is the mechanism of action of fast rTMS?
- > 5Hz
- stimulatory to underlying neurons
- causes the targeted area to be more likely to fire
How does transcranial magnetic stimulation (TMS) and rTMS work?
Magnetic coil turns on and off
- induces electrical current within the bain (which works on electrochemical basis)
- > firing - depolarisation of neurons
What are the key issues of the magnetic coil in TMS and rTMS?
- 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)
What is the mechanism of action of rTMS?
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
What is the most studied paradigm with repeated transcranial magnetic stimulation (rTMS)?
Depression
- characterised by underactivation of certain parts of the brain
What is the neurophysiological principle characterised in the underactivation model of depression?
Hypoactive dorsolateral PFC and connected deeper limbic areas (striatum, thalamus, anterior cingulate cortex)
How is repeated transcranial magnetic stimulation (rTMS) used for depression?
Fast rTMS
- stimulatory -> enhances the functions
- targets left side of dorsolateral PFC
- limbic system out of reach with this tool
What explains the choice of the current typical paradigm of rTMS for depression?
Optimal parameters are still unknown
What is the effectiveness of rTMS for depression?
- 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
How is rTMS used for psychosis?
Commonly, to treat auditory verbal hallucinations
How is rTMS used for auditory verbal hallucinations?
Neurophysiological principle of overactive speech network
- > slow rTMS applied to temporoparietal junction (left or right)
- > inhibits this network
What explains the choice of parameters in a typical paradigm of rTMS for auditory verbal hallucinations?
Data are missing to inform on what the optimal parameters would be
What is the effectiveness of rTMS for auditory verbal hallucinations?
Recent meta-analysis demonstrate a weighted effect size of 0.44
-> modest but statistically significant effect
For which interventions has rTMS shown therapeutic promise?
- Depression
- Auditory verbal hallucinations in psychosis
- Anorexia
- Bulimia nervosa
- Substance misuse
- Gambling disorders
- > re-regulating dysfunctional frontotemporal-limbic impulse control
Can we regulate the cognitive control of emotion through neuromodulation?
Possibly, but current data still quite limited
What is the mechanism of action of transcranial direct current stimulation (tDCS)?
- 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
What characterises the protocols of transcranial direct current stimulation (tDCS)?
Protocols less well-established than rTMS
- less spaciously focused
- typically 20 minus continuous application
- frequency of sessions vary
Which major areas have been explored with transcranial direct current stimulation (tDCS)?
- Depression
- Hearing voices
- Cognition
Which neurophysiological principle is targeted with transcranial direct current stimulation (tDCS)?
Underachieve PFC
-> tDCS tries to enhance brain plasticity
What is the effectiveness of transcranial direct current stimulation (tDCS)?
- 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
What is the principle of vagal nerve stimulation (VNS)?
Stimulate peripheral cranial nerves
-> get the current to pass back into the brain and hit regions
What is the mechanism of the vagal nerve stimulation (VNS)?
- 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
How is vagal nerve stimulation applied?
Lithium battery generator is surgically inserted
- stimulation applied on and off, targeting vagus nerve
What are the key issues with the research on vagal nerve stimulation (VNS)?
- 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
What is the principle of trigeminal nerve stimulation (TNS)?
- Stimulation of external nerve
- Get a current to go back into the brain to change brain functioning (similar to VNS)
What is the trigeminal nerve?
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
What make trigeminal nerve stimulation (TNS) non-invasive?
It stimulates the nerve externally
- 2 saline-soaked electrodes are placed on the forehead
What are the key issues of trigeminal nerve stimulation (TNS)?
- 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
What is the current use of deep brain stimulation (DBS)?
- 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)
What makes deep brain stimulation (DBS) an invasive technique?
- Brain surgery is needed (reversible)
- Neurosurgical implantation, under general anaesthetic, of 2 electrodes that will stimulate very specific brain regions
- Stimulators are implanted subclavicularly
What are the key issues with deep brain stimulation (DBS)?
- 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
Which brain areas are considered in deep brain stimulation (DBS)?
- Subgenual cingulate cortex
- Rostral cingulate cortex
- Inferior thalamic peduncle
- Ventral striatum / nucleus accumbens
- Lateral habenula
What are the research difficulties in the treatment protocols of neuromodulation techniques?
- 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
What explains the consistency between different protocols of neurmodulation techniques?
Studies are based on earlier research undertaken
-> no real biological rationale
What is the main question regarding the challenge of diagnostic criteria and use of neuromodulation?
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
What is the issue with the mechanisms of neuromodulation?
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
How acceptable is neuromodulation to patients?
- 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
What is the cost and access of neurmodulation?
- 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
What is the main factor in the cost of neuromodulation?
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
