TMS reading Flashcards
TDCS can only produce small electrical currents - not enough to generate AP in humans. what does it do instead.
it polarises neuron’s
- changes transmembrane electrical potential by 0.5-1mV
- now harder/easier for neurons to fire with ongoing brain activity
what is the principle of electromagnetic induction?
- change in electromagnetic field
- gives rise to companion electric field
- induces electrical current in nearby conductors
TMS - explain the basics
- large pulse of current in external stimulating coil
- current rises and falls from 1 Tesla or more (up to 2 Tesla) within 1ms
- generates electromagnetic field that penetrates the skull and scalp with little impedance
- the electrical field induced causes currents to flow in brain
Why was TMS better than Merton and Mertons method?
- electrical current induced = smaller
- similar in magnitude to ones brain produces itself
how much of the brain is stimulated with a figure of 8 coil
- stimulates area of half a cm squared (according to miss) and 2-4cm (According to rothwell reading)
what affects the depth of the stimulation with TMS (limitation)
- how far away the coil is from n
- coil 30% effective when 5cm away
- lot of distance between = no effect
- different designs of the coil could increase depth but at the expense of focality
- also worth noting that superficial structures would be more stimulated than those deeper
How did TDCS emerge
Emerged from animal studies
- where they found the DC polarisation of the exposed cortex could increase or decrease ongoing activity
- several minutes of stimulation - led to lasting effects of excitability
- 10 mins of polarisation - discharge rates increased or decreased for hours or more
What’s gwarning under the anode vs cathode
- If cortical surface was smooth
- Under anode: neurons located perpendicular to scalp - depolarised at cell body. makes them easier to fire with ongoing synaptic activity
- Under cathode: reduces the excitability of neurons
How could we study connectivity using TMS
- well if you stimulate motor cortex and muscle contracts = confirms existence of pathway
- can then play around with it to investigate how well a pathway operates using properties of the connection
- e.g., in multiple scerlosis the pathway from the cortex to the muscle is much slower. this is bc of demyelination.
- we can apply this concept to studying the connection between different anatomical sites in the cortex
2nd way
- pair TMS with different technique e.g. fMRI or EEG
- E.g., study stimulated motor cortex and found other brain areas activated - BG, cerebellum and thalamus
Why is it a problem to study connectivity using TMS
- bc the connection between regions becomes stronger when tested with TMS
- n’s current state affects the spread of activation - activity with stimulation spreads MORE if n more alert
TMS, TDCS and plasticity
Studies have shown
- rTMS or 10 mins or more of TDCS
- affects on the cortex outlast the period of stimulation by minutes-hours
- this is bc stimulation interacts with synaptic plasticity
- increases/decreases the excitabiltiy of connections in a manner similar to LTP/LTD
- can be used then for neurorehabilitation
how might rTMS and TDCS induce plasticity
- rTMS - repeated pulses activate the same set of synaptic connections in turn leading to long term changes in connections efficacy
- for TDCS the mechanism is less clear - since TDCS doesn’t actually discharge neuron
- plastic effects are dependent upon activity during TDCS
- In animal experiments, this has been shown to cause brain derived neurotrophic factor (BDNF)-dependent increases in synaptic efficacy (Fritsch et al., 2010).
how could we improve present methodologies of brain stimulation to reduce the variation in response both between individuals and on the same individual from day to day
- 1) the effects of the stimulation depend on the brain state at the time stimulation is applied
- could: control the brain state (e.g. by some focussed behavioural task)
- apply stimulation only when brains in certain state (e.g., by patterns of EEG activity, may be one approach that will improve responsiveness (Goldsworthy et al., 2016))
- 2) both TMS and TDCS activate different types of neurone
- e.g. excitatory vs inhbitory, or interneurones versus projection neurones
- methods to make TMS/TDCS more selective
- TMS: examining changes in the pulse waveform of stimulation to match the best form to activate particular types of neurone
- TDCS: increasing its focality by stimulating through multiple electrodes in order to achieve a more focal field in the brain (D’Ostilio et al., 2016).
what does TDCS do
tDCS specifically applies a constant current to the brain in order to produce a sustained polarisation of neural membranes.
developing the TDCS technique: tRNS
- transcranial random noise stimulation (TRNS)
- new version of TDCS
- applies current btw 1-2mA
- alternates currents at frequencies similar to those seen in ongoing EEG e.g., 10Hz equating to the EEG alpha rhythm or 20Hz equating to the beta rhythm
- such currents are capable of entraining oscillating activity in neural populations at the applied frequency in animals. It is thought that the same may occur in the human brain (Ali et al., 2013)
- Such entrainment of brain activity can modulate or even suppress ongoing tremor activity in patients with Parkinson’s disease (Brittain et al., 2013)
- other studies examined the role of frequency coupling in governing the interaction of distant areas during cognitive tasks - e.g., frontal and parietal areas of cortex = synchronised at 6Hz when performing working memory task. artificial synchronisation of activity at this frequency with tACS can improve performance on the task, suggesting that it might be possible to enhance interaction between brain areas (Polania et al., 2012).
developing the TDCS technique: focused pulsed ultrasound
- better than TMS and tDCS - as can be focussed onto targets deep in the brain
- Neurosurgeons use focussed US to heat very small volumes of brain to produce permanent lesions
- a recognised method for producing small lesions in the thalamus to treat tremors (Elias et al., 2016)
- If a different frequency of US is applied, evidence from animal experiments show it can stimulate neurones rather than destroy them (Tufail et al., 2010)
- If safety concerns can be satisfied, it may, therefore, become possible in the future to use focussed US to directly activate regions deep in the brain that are currently inaccessible to TMS and tDCS
what ensures blinding success in the active vs SHAM condition
what would this help us clarify?
solving the technological challenge of giving sham n the same acoustic and sensory effect without any brain stimulation.
The use of surface electrodes for skin stimulation in combination with a shielded TMS coil seems the current gold standard
helps clarify
- effects caused by neural manipulation
- effects caused by sensory side effects
what side effects are caused by the coil
- loud clicking noise
- stimulates skin - resulting in somatosensory effects
- e.g. peripheral nerve stimulation / evokes face muscle twitches
what are the problems of sensory side effects?
auditory and sensory effects may
- distract n
- influence spatial attention
- influence alertness
- placebo effect due to the tingling - charlie with the pill
- their expectation of brain stimulation might be that it causes specific behavioural or cognitive changes which they unconsciously carry out
describe the two SHAM conditions for TMS
- can turn coil on its side - auditory effects and magnetic field is strong enough to induce somatosensory effects
- use imposter coil - looks like normal coil but has a magnetic shield that attenuates the magnetic field
- this one has auditory effects only - big problem the lack of sensation will give away its a sham
why is a SHAM condition particularly useful for TMS
helps us seperate sensory/placebo effects from real ones
what is an effective SHAM condition
- give the imposter coil with the magnetic shield
- WITH surface electrodes to stimulate the skin - time-locked to each time a pulse is delivered (click)
- OR stimulating a different site that is not relevant to the tas
- both anatomical and sensory effects
key thing the experience of the TMS stimulation needs to be the same for n in both groups
what’s a general problem with TMS work concerning the placebo effects?
NON CLINICAL STUDY
- hardly any studies have looked into the placebo effects of TMS
- really silly considering TMS is widely used to investigate all kinds of mental phenomena
- only one study looked into this and found no placebo effects (Jelić et al., 2013)
- just bc of this 1 null result - doesnt mean placebo effects dont exist in TMS
whats a general problem with TMS research concerning the blinding effects of active vs SHAM stimulation
NON CLINICAL STUDIES
- success of blinding n - received hardly any attention
- bare sham-controlled studies have been published but hardly any of them report the blinding sucess
- most researchers seem to be very aware of the limitations of most sham TMS approaches and rather not expose a possible confound of their study by not collecting any data on blinding success and how the stimulation was experienced
- obtaining such empirical data is vital - explicitly facing this issue allows entire field to progress to higher-quality sham TMS approaches.
what placebo effects have been observed in TMS research
CLINICAL STUDY
placebo effects have indeed been observed in many TMS treatment studies for various brain-related disorders including
- major depression (Brunoni et al., 2009),
- epilepsy (Bae et al., 2011),
- obsessive-compulsive disorder (Mansur et al., 2011),
- and Parkinson’s disease (Okabe et al., 2003).
Any evidence of blindings success in TMS?
CLINICAL RESEARCH
Data on blinding success is rarely reported
- two recent reviews addressed this issue albeit based on a rather small number of studies (Broadbent et al., 2011; Berlim et al., 2013).
- both reviews - no sig difference in n guessing htey were in the SHAM or active group
- but studies sometimes failed to maintain blinding integrity
what % of randomized sham-controlled clinical trials reported data on blinding success?
less than 15% - unclear whether researchers often withhold this information in case of blinding failure (Broadbent et al., 2011)
Does TMS have blinding success?
- does have blindings sucess in clinical settings - between group treatment studies
- does not have blinding sucess in basic research
- within group designs = more common and n here are more likely to descern the real from sham condition
What is the gold standard for a TMS control and has this bene shown sucessful?
- electrical stimulation of the skin results in somato-sensory effects very similar to active TMS if the stimulation intensity is individually calibrated (Arana et al., 2008; Borckardt et al., 2008; Mennemeier et al., 2009)
- skin sensation is more electric so that experienced participants might be able to discriminate the two
- while naive n cannot distinguish the two experienced n can (Rossi et al., 2007; Mennemeier et al., 2009).
SHAM TMS needs work. An interesting alternative to current approaches could be to apply electrical stimulation also during active TMS
Is the SHAM TMS condition approved for all populations?
- for basic research - needs work
- for clinical setting with naive n - sound
If we sucessfully blind n to which condition they are in (sham vs active) does that cancel out any placebo effects
- nope because individual n might have different beliefs on what they expect to happen
- these expectations could differ depending on the intensity of the stimulation they recieved which is hard to match across n
- differences in hair thickness, head fat, the structure and electrical conductivity of the scalp, skull, and meninges, and the orientation of neurons within cortical layers are likely to result in different current paths and a different susceptibility to depolarizing currents
what have we learned looking at Deuker and Sack’s (2013) study on sham TMS?
Observed differences between TMS target sites or time points do not necessarily arise from the neural effects of TMS.
how do the sensory side effects of TMS influence task performance
- hardly any research on this - hard to know what the control group is controlling for - makes it harder to evaluate their adequacy
Duecker and Sack, 2013
- used a sham TMS coil to investigate the sensory side effects of TMS on behavior without potential confounding due to neural effects of TMS
- applied sham tms over the left or right hemisphere before presenting visual target in the left or right hemifield
- lateralized sham TMS pulses caused automatic shifts of spatial attention toward the position of the TMS coil thereby facilitating target detection in the corresponding hemifield
- so sensory side effects can influence performance depending on exact location n hear the pulse
Duecker et al., 2013
- applied either single-pulse sham TMS or active TMS over the vertex, a stimulation site where neural effects are typically not expected, and explored potential changes in task performance
- detection task and angle judgment task
- found highly specific sensory side effects that were dependent on a complex interplay of the task, type of stimulation, and time point of stimulation.
research should look more into the effects of SHAM tms
- considering it not simply one of many control strategies but informative in itself with its unique contribution to the development of TMS methodology
Why might approaches controlling activive TMS not be 100% good
Generally fail in case of highly specific sensory side effects of TMS simply because either the stimulation site or stimulation time point is not kept constant
one exception = manipulating the TMS coil orientation which results in changes in the induced electric field without acoustic or somato-sensory differences between TMS conditions (Thielscher et al., 2011).
However, it is by no means guaranteed that this approach always results in differential effects and it requires detailed knowledge regarding optimal TMS coil positioning
Studies with controls often just have the sham coil but why wouldnt this be an effective control in a study suing TMS to show a region is active at a certain TIME
- TMS can show a region is functionally relevant at a particular point in time during task execution.
- To make such a claim, need to show that the same effects do not occur when stimulating another brain area OR time point.
In this sense, TMS experiments always require an active TMS control condition, and sham TMS approaches can never be sufficient as they fail to demonstrate such specificity.
what do Duecker and sacks (2015) conclude for the future of SHAM TMS research
We need a complementary use of sham TMS approaches,
- to controlling for the sensory side effects of TMS, alongside active TMS control strategies
- A typical TMS experiment should therefore consist of multiple stimulation sites or stimulation time points using active TMS.
- Sham TMS can then be used as an orthogonal control condition, essentially copying all stimulation parameters (esp location stimulated).
Why do we need SHAM TMS?
To control for the placebo and sensory side effects of TMS
how to cognitive neuroscience studies use TMS and TES differently?
- TES: neuromodulatory approaches to induce plasticity
- TMS: does this and suprathreshold stimulation used to disrupt activity
What are transcranial electrical stimulation methods (tES)
- transcranial direct current stimulation (tDCS)
- transcranial alternating current stimulation (tACS)
- transcranial random noise stimulation (tRNS)
Are the major findings of TMS on solid grounds?
- Yes, highly replicable findings in many domains including the effects of TMS on the perception of movement, language, perception, preparation and production of action = highly replicable
- even studies looking at the communication of sites - FEF and R.PPC have produced highliy replicable findings
What is the most recent development of TMS research in recent years
The successful migration of TMS to the ventral stream
- reveals role of the fusiform and occipital face areas, the lateral occipital area, and the extrastriate body area in face and body perception
- replicable findings
Urgesi et al., 2004, Urgesi et al., 2007, Dzhelyova et al., 2011, Pitcher, 2014, Pitcher et al., 2007, Pitcher et al., 2008, Pitcher et al., 2009, Pitcher et al., 2011a, Pitcher et al., 2011b, Pitcher et al., 2012, Mullin and Steeves, 2011, Silson et al., 2013).
What is a problem with TMS parameters?
- no set criteria on the parameters to use
- we have generally agreed on the level of stimulation
- but not agreed on: stimulus timing, frequency and localisation
theta bust paradigms
Theta burst paradigms - are used to study cognitive functions in a pure disruptive manner (e.g., Vallesi et al., 2007, Ko et al., 2008)
- continuous theta burst = longer term inhibitory effects
- Intermittent theta burst = excitatory effects (Huang et al., 2005).
Different types of rTMS?
Figure from Dayan et al., 2013.
