1
Q
TDCS can only produce small electrical currents - not enough to generate AP in humans. what does it do instead.
A
it polarises neuron’s
- changes transmembrane electrical potential by 0.5-1mV
- now harder/easier for neurons to fire with ongoing brain activity
2
Q
what is the principle of electromagnetic induction?
A
- change in electromagnetic field
- gives rise to companion electric field
- induces electrical current in nearby conductors
3
Q
TMS - explain the basics
A
- 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
4
Q
Why was TMS better than Merton and Mertons method?
A
- electrical current induced = smaller
- similar in magnitude to ones brain produces itself
5
Q
how much of the brain is stimulated with a figure of 8 coil
A
- stimulates area of half a cm squared (according to miss) and 2-4cm (According to rothwell reading)
6
Q
what affects the depth of the stimulation with TMS (limitation)
A
- 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
7
Q
How did TDCS emerge
A
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
8
Q
What’s gwarning under the anode vs cathode
A
- 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
9
Q
How could we study connectivity using TMS
A
- 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
10
Q
Why is it a problem to study connectivity using TMS
A
- 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
11
Q
TMS, TDCS and plasticity
A
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
12
Q
how might rTMS and TDCS induce plasticity
A
- 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).
13
Q
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
A
- 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).
14
Q
what does TDCS do
A
tDCS specifically applies a constant current to the brain in order to produce a sustained polarisation of neural membranes.
15
Q
developing the TDCS technique: tRNS
A
- 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).
16
Q
developing the TDCS technique: focused pulsed ultrasound
A
- 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
17
Q
what ensures blinding success in the active vs SHAM condition
what would this help us clarify?
A
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
18
Q
what side effects are caused by the coil
A
- loud clicking noise
- stimulates skin - resulting in somatosensory effects
- e.g. peripheral nerve stimulation / evokes face muscle twitches
19
Q
what are the problems of sensory side effects?
A
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
20
Q
describe the two SHAM conditions for TMS
A
- 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
21
Q
why is a SHAM condition particularly useful for TMS
A
helps us seperate sensory/placebo effects from real ones
22
Q
what is an effective SHAM condition
A
- 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
23
Q
what’s a general problem with TMS work concerning the placebo effects?
NON CLINICAL STUDY
A
- 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
24
Q
whats a general problem with TMS research concerning the blinding effects of active vs SHAM stimulation
NON CLINICAL STUDIES
A
- 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.
25
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).
26
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
27
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)
28
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
29
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
30
Is the SHAM TMS condition approved for all populations?
* for basic research - needs work
* for clinical setting with naive n - sound
31
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
32
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.
33
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
34
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
35
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.
36
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).
37
38
Why do we need SHAM TMS?
To control for the placebo and sensory side effects of TMS
39
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
40
What are transcranial electrical stimulation methods (tES)
* transcranial direct current stimulation (tDCS)
* transcranial alternating current stimulation (tACS)
* transcranial random noise stimulation (tRNS)
41
42
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
43
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).
44
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
45
Different types of stimulation the experimenter can give?
stimulation parameters
* Single pulse
* double pulse
* on-line repetitive pulse
* and off-line repetitive pulse
46
what are the two types of off-line repetitive pulse?
* theta burst
* and 1 Hz stimulation
47
What is the difference between stimulation parameters?
Differ in terms of
* physiological effects
* localization
* behavioral effects
* or safety profiles
48
What influences one's decision to use a certain freq of TMS stimulation over another?
* Whether you want excitatory or inhibitory effects
* and the type of behavioural effects being pursued
49
What effects do we see with single-pulse TMS vs repetitive 1Hz TMS
* Single-pulse TMS = largely excitatory effects (but may interact with initial cortical state and task requirements to result in inhibition e.g., [Waldvogel et al., 2000](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib154)
* Repetitive 1 Hz rTMS is widely used as an inhibitory intervention ([Chen et al., 1997](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib33)). associated with mimicking the effects of neuropsychological patients (e.g [Guse et al., 2010](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib63)).
50
TMS frequencies. what effects do these have (excitatory vs inhibitory)
* higher frequencies are commonly used in disruption studies - e.g. 5-10Hz
* not clear tho whether this has excitatory or inhibitory effects
* The effect partly depends on intensity
* low intensities tend to produce inhibition and higher intensities, facilitation ([Classen and Stefan, 2008](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib36)).
51
theta bust paradigms
Theta burst paradigms - are used to study cognitive functions in a pure disruptive manner (e.g., [Vallesi et al., 2007](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib150), [Ko et al., 2008](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib74))
* continuous theta burst = longer term inhibitory effects
* Intermittent theta burst = excitatory effects ([Huang et al., 2005](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib70)).
52
Different types of rTMS?
Figure from [Dayan et al., 2013](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib44).
53
Different variants of TBS stimulation
theta-burst stimulation (TBS)
* three 50-Hz pulses applied at 5 Hz for 20–40 s (continuous TBS, cTBS)
* or each burst is applied for 2 s and repeated every 10 s for 190 s (intermittent TBS, iTBS)
* intermediate TBS (imTBS), 5 s burst trains are repeated every 15 s
this is not all the possible ones
54
what yields information about the timing of psychological processes
Single- and double-pulse stimulation
example study - Pitcher et al., 2008
* investigated role of the right occipital face area (rOFA) and right [somatosensory cortex](https://www.sciencedirect.com/topics/neuroscience/somatosensory-cortex) (rSC)
* in the detection and embodiment of facial expressions
* rTMS applied during perceptual discrimination of facial expressions
* rTMS established the task selectivity of stimulation (expression discrimination, but not identity matching, was impaired)
* and location specificity (no effect of stimulation to non-face regions of somatosensory cortex).
55
What method gives us information about the timing of psychological processes
Single- and double-pulse stimulation
example study - Pitcher et al., 2008 - used rTMS to double pulse stimulation
* investigated role of the right occipital face area (rOFA) and right [somatosensory cortex](https://www.sciencedirect.com/topics/neuroscience/somatosensory-cortex) (rSC)
* in the detection and embodiment of facial expressions
* rTMS applied during perceptual discrimination of facial expressions
* rTMS established the task selectivity of stimulation (expression discrimination, but not identity matching, was impaired)
* and location specificity (no effect of stimulation to non-face regions of somatosensory cortex)
* Delivering double pulses of TMS at different times, established a temporal hierarchy in which the rOFA was important between 60 and 100 ms and the rSC at 100–140 and 130–170 ms
56
what are the key basis of a TMS experiment?
* task
* location
* timing
* controls on all 3 variables
* good study that showcases this = Pitcher et al., 2008
57
The cortical localisation of TMS. how can we be sure about the cortical specificity of the site stimulated? how important is getting this perfect too?
no absolute answer on this - depends entirely on the research question being asked and the power of the experiment
58
In what way can power affect the cortical localisation of TMS
Sack et al., 2009
* examined effect of TMS over right intraparietal cortex on numerical processing
* compared 4 methods of TMS localisation to locate the region of interest
1. **individual functional MRI (fMRI-guided TMS) neuronavigation;** 5 n needed to observe a significant effect of TMS
2. **Individual MRI guided TMS neuronavigation**; 9 n needed
3. **group functional Talarich coordinates;** 14 n needed
4. **the 1-20 EEG position P4;** 47 needed
all methods were valid and accurate cortical localisation. of the area differed in terms of power
59
State dependent TMS - how do we know when a region is excited?
* motor studies know the level of excitability in the motor cortex from the MEP
* very good because both within and between n - effects of TMS differ depending on the state of excitation in the brain tissue being stimulated
* but in cognitive studies - no measure of the state of excitation of the PPC, FEF, DLPC, OFA and other favorite sites
60
What ways have people taken to define stimulation levels? what does this not account for
* measuring the thickness of the skull
* distance between coil and cortex
* then stimulating at percentage of motor threshold (Stokes et al., 2007) - but there is no way knowing the stimulation threshold of a region using M1 (Stewart et al., 2001)
Doesnt account for the effect of the brain state during stimulation.
61
State dependent paradigm
what methods have people undertaken to influence the initial state of the region being stimulated?
Silvanto's paradigm used adapotion to influence the region's initial state.
Silvanto et al., 2007
* n adapted to colour/orientation combinations for 30s
* subsequently asked to report the colour of test stimuli
* TMS delivered during presentation of some test stimuli
* without TMS - reporting bias to the complementary colour of the adaptation
* with TMS over visual cortex - n reports were bias to the original adapting stimulus colour
so he was able. toplay with the neurons as. afunction of the initial state they were in.
62
State-dependent paradigm
prove its utility
Cattaneo et al., 2012
* adapting region if visual field → impaired mental imagery in that region of space
* inhibition unmasked with TMS to occipital visual cortex
Silvanto and Soto (2012)
* TMS facilitated performance on a short term memory task
* study provides physoological rationale for an enhancement effect in a TMS experiment
* lots of studies have shown enhancment effects of TMS but few are grounded in physiology
63
What type of state does state dependency depend on?
both memory states and perceptual states
Soto et al., 2012
* n had to search for a target preceded by a colour cue that had to be remembered (memory condition) or attended to (priming condition)
* TMS during the memory state enhanced performance
* TMS during the attention state inhibited performance
64
State-dependent paradigm
Describe a higher order study looking at this
Cattaneo et al., 2010
* investigated category-specific neuronal representations in the encoding of tool words in the left ventral pre-mortor cortex (PMv)
* n primed with a category name either “tool” or “animal" to adapt PMv to the category objects
* TMS applied at the onset of a target (test) word either congruent or incongruent to primed category
* TMS interacted with the previous stimulus exposure and abolished the priming effect
65
State dependence is an important methodological factor to be taken in cognitive experients. Why?
studies have shown that the previous state of n influences the sitmulation effects
66
How do we currently understand the mechanisms of state dependency?
as an interaction between the induced level of activity by the adapting stimuli and the electrical stimulus delivered by TMS
Best available explanation offered by [Dayan et al. (2013)](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib44) and [Silvanto et al. (2008)](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib131):
TMS affects excitatory and inhibitory populations differently and the effects of adaptation operate mainly on changing the suppressive effect of inhibitory populations
Pasely et al., 2009
* measured spike and field potential activity as a function of spontaneous discharge rates
* the variability in response is explained at least partly by the state dependent effects
* specifically, higher activity before TMS predicts greater responses to the stimulation
67
whats the best way to determine the intensity of sitmulation?
well you have three options
* Stimulate all n to same intensity
* stimulate n to same intensity to that of the motor threshold
* sitimulate n at an intensity modified by calculating the distance from the coil to the cortex
last one is best but as we know from state dependency research this added precision is illusory
68
Lets say you use MRI for all n, calculate their MEP and then the distance between the coil and head. and THEN calculating the “correct value”.
what is still a problem here
the assumption that the MEP threshold means anything anywhere else in the brain
69
What's the big problem with methods that determine the intensity of stimulation?
* we dont know which is best
* dont know what a given level of stimulation means in terms of cortical disruption
70
how much stimulation do you deliver with TMS?
On this simple question—how much stimulation to deliver—rests a lesson about all TMS disruption experiments.
The lesson is this: the value of the inferences made in any TMS disruption experiment is a function of the controls within that experiment.
71
what affects the value of inferences drawn from TMS research?
* controls within the expeiriment
* quality of control site used
*
72
What is the common control site used in TMS
* vertex - but this is a control for noise, twitches, and some cortical activity
* better inferences about location specificity can be made if a control site is active and part of the circuit
this is bc
1. stimulating part of the same circuit may reveal inter-aerial or inter-hemispheric interactions ([Battelli et al., 2008](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib7), [Plow et al., 2014](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib109), [Duecker et al., 2013](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib48)).
2. a control in the same circuit is often nearby on the cortex and is therefore a good control for scalp sensations and noise ([Tadin et al., 2011](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib144)).
3. provides the most stringent test of claims of localization of function ([Vangeneugden et al., 2014](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib152)).
https://www.sciencedirect.com/science/article/pii/S1935861X15011298
73
what have people combined TMS with?
fMRI and EEG
74
TMS and EEG
* popular. instudies of vision and attention
* used to examine effects of TMS on phyisiological activity
* as well as to study the importance of pre-stimulus activity on the perception of real stimuli or TMS induced phosphese
75
TMS and EEG: Romei et al., (2008)
demmonstrated a causal relationship between
* pre stimulus cortical state
* sensitivity of occipital cortex TMS that would induce phosphene perception
before TMS stimulation: n in low alpha state were more likely to see phosphenes compared to those in high alpha state
76
Why is the combination of TMS and EEG particularly sick?
Bc of the temporal resolution of TMS and EEG.
* very effective way to study pre-stimulus state effects
77
how can TMS-EEG be used to:
study the physiological effects of TMS-induced perception
(EVALUATION POINT FOR EEG!!!)
Taylor et al., (2010)
* applied TMS to occipital cortex - can you see phosphenes?
* compared n responding yes or no they can see them
* found post-TMS electrophysicological effects were seen after only 160ms
* this is quicker than the effects following real visual stimuli in the brain
* rly cool finding - means the effects of TMS induced perception = earlier than those when you physically see them
78
TMS-EEG: reveal subsequent effects of TMS on electrophysiological activity
Sadeh et al., (2011)
* presented face or body part stimuli to n
* TMS - either OFA or extrastriate body area (EBA) in double pulse pairs of 60ms and 100ms post face/body onset
results
* double dissociation
* OFA TMS changed the N1 component for the body but not face stimuli
* EBA TMS changed the N1 component for body not face stiuli
79
Why is are combination studies e.g. TMS-EEG better than single method studies?
E.g., Sadeh et al., 2009.
Thinking through the temporal and spatial aspects of a problem in cogntiive neuroscience can produce a body of replicable work, across laboratories, which cannot be achieved by any single method.
80
TMS-fMRI - what are the three ways to combine these?
1. online: TMS applied in the scanner (technical challenges of simultaneous method)
2. offline:TMS applied immediately before n nenter scanner (no technical challenges)
3. TMS and [ligand binding](https://www.sciencedirect.com/topics/neuroscience/ligand-binding) studies using [positron emission tomography](https://www.sciencedirect.com/topics/neuroscience/positron-emission-tomography) (PET)
81
What was Sack' (2010) critique of TMS-fMRI combined studies
* Techniqcal challenges of online TMS-fMRI study
* in past n stimulated in the scanner, experiments today looking at prev studies either confirm findings or report activation of areas distal from the site stimulated
* E.g., Sack (2007) stimulated the parietal cortex while n carried out visuospatial task in scanner.
* resulted in clear **right hemisphere frontoparietal network** of areas associated with visuospatial functions
* The value of simultaneous TMS-fMRI rests on two main features: **distal effects of the stimulation** that may implicate effects caused by changes induced elsewhere than the target site of stimulation, and **state dependenc**e ([Bestmann and Feredoes, 2013](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib10))
* All the major issues in concurrent TMS-fMRI have been addressed in [Siebner et al. (2009)](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib127), a comprehensive consensus paper, and [Bestmann and Feredoes (2013)](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib10).
82
why can we use more complex cognitive designs and hypotheses with offline TMS-fMRI method combination
bc its released from the technical challenges of simultaneous TMS-fMRI
83
Describe a study using offline TMS-fMRI method
[Pitcher et al., (2014)](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib108)
* looked at processing of faces
* specifically invariant (never changing) dynamic information about faces
* investigated functional interactions between regions of the **ventral visual cortex**
* disrupted processing in the **rOFA** and **right posterior** [**superior temporal sulcus**](https://www.sciencedirect.com/topics/neuroscience/superior-temporal-sulcus) **(rpSTS)** using theta burst TMS _before_ n being presented with dynamic or static faces.
results - double dissociation
* TBS of → rOFA diminished the activity in response to static but not dynamic
* TBS of → rpSTS reduced the response to dynamic but not static faces
This dissociation showed that dynamic and static facial information relies on separate anatomical pathways.challenges current views of face perception, which suggest that all face information is relayed via the OFA. This study shows that some dynamic facial information indeed bypasses the OFA.
84
TMS and [ligand binding](https://www.sciencedirect.com/topics/neuroscience/ligand-binding) studies using [positron emission tomography](https://www.sciencedirect.com/topics/neuroscience/positron-emission-tomography) (PET).
studies have been able to show detailed cortical to subcortical distal effects.
For example, stimulation of the [dorsolateral prefrontal cortex](https://www.sciencedirect.com/topics/neuroscience/dorsolateral-prefrontal-cortex) (DLPFC) produced changes in [dopamine release](https://www.sciencedirect.com/topics/neuroscience/dopamine-release) in the [caudate nucleus](https://www.sciencedirect.com/topics/neuroscience/caudate-nucleus) or in the putamen after stimulation of the motor cortex ([Strafella et al., 2001](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib141), [Strafella et al., 2003](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib142)).
85
why would you want tMS to induce cortical plasticity?
allows one to study behavioral change and to induce change that may have clinical value.
86
using TMS to induce plasticity - depends on…?
many factors that interact with brain stimulation including age, attention, sex, physiological state, genetics, and time of day
87
Can TMS or tES induce plasticity?
[Ridding and Ziemann (2010)](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib111) have identified all the major factors in this field and rightly state that “even in neurologically normal subjects the variability in the neurophysiological and behavioural response to such brain stimulation techniques is high.”
88
Example of TMS study with good plastic effects?
[Agosta et al. (2014)](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib1)
* patients with chronic stroke - visutal extinction. TMS successfully alleviated visual extinction
* by applying low-frequency TMS (assumed to be inhibitory) over the left, intact parietal cortex.
* The idea, using a “push-pull” model of inter-hemispheric interactions, is that by inhibiting the intact [parietal lobe](https://www.sciencedirect.com/topics/neuroscience/parietal-lobe), the damaged hemisphere would suffer less from the inhibitory competition of the intact hemisphere.
89
what is worse about tES compared to TMS
TMS methodology has reached a level of maturity signaled by standard procedures, replication, integration with other techniques and constraints on explanations of data.
Same claim cannot be made for tDCS or tRNS.
90
What are the three goals of using tES in cognitive neuroscience
1. functional localisation
2. understand the physiological mechanisms of these effects
3. enhance cognitive function
91
What was Carl Sagan’s warning
That “Extraordinary claims require extraordinary evidence.”
92
Three types of tES
1. tDCS is mainly used to modulate excitation and/or inhibition, and to improve and in some ways alter cognitive functioning
2. tACS, on the other hand, is mainly used with the goal of changing oscillatory brain states
3. tRNS is used to induce excitation and resulting plasticity ([Chaieb et al., 2011](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib32), [Terney et al., 2008](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib147))
93
whats the literature on tDCS tACS and tRNS saying
literature in tDCS is large and growing, the literature is tACS and tRNS is limited
94
some questions we need to ask when evaluating tES studies
1. what is an adequate control stimulation condition?
2. What are the effects of the intensity of stimulation?
3. What are the effects of montage placement?
95
what four things do researchers assume with tES studies?
* Polarity
* Intensity,
* Duration,
* Montage
96
Researchers in tDCS research assume the polarity of activity. why is this wrong
Assume that anodal stimulation is always excitatory and cathodal stimulation is always inhibitory (see [Horvath et al., 2015a](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib68)).
[Bestmann et al. (2015)](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib14) have given a detailed account of why this cannot be the case.
* yes theres a common direction between polarity dependent tDCS changes are directional
* but under the electrodes the ffect of this directional flow is not uniform ([Batsikadze et al., 2013](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib6))
* stimulation interacts with diff cell morphologies and cortical surface shapes create inhomogeneities that in turn change the net effects of stimulation ([Bestmann et al., 2015](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib14)).
need to approach the link between assumed physiology and behavioral effects with caution.
97
Researchers in tDCS research assume the polarity of activity. why is this wrong
Assume that anodal stimulation is always excitatory and cathodal stimulation is always inhibitory (see [Horvath et al., 2015a](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib68)).
[Bestmann et al. (2015)](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib14) have given a detailed account of why this cannot be the case.
* yes theres a common direction between polarity dependent tDCS changes are directional
* but under the electrodes the ffect of this directional flow is not uniform ([Batsikadze et al., 2013](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib6))
* stimulation interacts with diff cell morphologies and cortical surface shapes create inhomogeneities that in turn change the net effects of stimulation ([Bestmann et al., 2015](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib14)).
need to approach the link between assumed physiology and behavioral effects with caution.
98
assumtions: the effects of tES intensity
(and duration ?)
another reason not to trust that tES operates on a see-saw of excitatory and inhibitory
In cognitive tES studies tend to take findings from MEP studies and assume that they transfer to regions outside the motor cortex, but - use findings easy to deal with
for example
* many studies assume a linearity of stimulation effects from 1 to 1.5 to 2 mA
* not true
* in tES - as the stimulation intensifies from 1-2mA the **direct current loses its opposing polarities**
* results in cathodal stimulation inducing excitatory effects
problem bc anodal effects in cognitive studies are routinely interpreted as being due to excitation and cathodal effects due to inhibition ([Boggio et al., 2010](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib18), [Chi et al., 2010](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib35), [Fecteau et al., 2007](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib57), [Hecht et al., 2010](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib66)).
99
What. isa problem of tES research iregarding the suration of effects
effects of 2 mA emerge after only 90 min and it is reasonable to ask
how many times have effects been missed in studies (cf. [Agosta et al., 2014](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib1)) by not continuing to measure effects for longer periods.
100
Assumptions: the electrode montage (the reference)
* in cognitive studies - most common electrode montages are a bilateral, homotopic arrangement or a reference over the frontopolar cortex
* 2 problems with this
1. whether regions stimulated in each hemisphere, say left and right PPC or left and right PFC, will interact.
2. The frontopolar cortex is not a dormant site in cognitive terms
remarkable number of studies interpret their findings as if the effects are due to pure excitation/inhibition under the electrodes, ignoring any interaction between the two sites
101
Minimum Conditions for Execution and Interpretation for a tES Experiment
* control sites
* control task
* intensity
* duration
* montage
* polarity
* effect robustness
102
Minimum Conditions for Execution and Interpretation for a tES Experiment: control site
stimulation vs no stimulation = weak method
instead use a control site
Control polarity may be sufficient here - allows for specific claims about the site to be made
103
Minimum Conditions for Execution and Interpretation for a tES Experiment: *Control Task*
needs a control **task** that shows the effects observed are specific to _experimental task components_
Consider that there are effects of tDCS on, say, decision making following stimulation of the DLPFC.
* The DLPFC is involved in several functions, including working memory.
* need to establish - effects on decision making are separate from any possible effects on working memory
* to do this would require a working memory control task.
104
Minimum Conditions for Interpretation for a tES Experiment: *Intensity*
Currently no guidlines on the stimulation based. onsaftey studies in M1
* The assumption that intensity simply summates is clearly not tenable.
* if experimenters wish to be able to make statements about excitatory or inhibitory effects
* should limit their stimulation levels to those with known effects in the motor cortex
reccomended by primer paper
105
Minimum Conditions for Interpretation for a tES Experiment: *Duration*
As with intensity, the effects in M1 do not simply summate with increasing duration.
* The case for matching effects with known motor effects is the same here as for intensity,
* but the major caution is that even in making comparisons with M1, one cannot justify the assumption that cortex outside M1 will respond in the same way to changes in intensity or duration
106
Minimum Conditions for Interpretation for a tES Experiment: montage
Perhaps this is the greatest minefield because:
the effects of montages (other than the M1 montages)
can only be indirectly inferred.
There are many reasons to try new electrode sizes, numbers, and montages, but until we know something about the effects of these variables, it is important to interpret the physiology conservatively or not at all as a causal factor in behavioral effects.
107
Minimum Conditions for Interpretation for a tES Experiment: polarity
The polarity of stimulation can only be inferred where the montage conforms to parameters established in studies of M1 excitability.
[_Jacobson et al. (2012)_](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib72) carried out a meta-analysis of the literature and observed that while the effects of anodal stimulation in cognitive studies are often facilitatory, there is no reliability in the symmetry of polarity and cathodal stimulation
108
*Minimum Conditions for Interpretation for a tES Experiment: Effect Robustness.*
There is a clear distinction to be made concerning whether effects are scientifically interesting or of clinical value – the two goals are different.
* small effect obtained during the course of an experiment = scientifically interesting.
* for clinical relevance, however, the effect must be robust over hours, days, weeks, or months.
109
Application of tDCS on addictive behaviour
lack of effective pharmacological interventions in most forms of drug addiction, especially addiction to [psychostimulants](https://www.sciencedirect.com/topics/neuroscience/psychostimulant) ([Phillips et al., 2014](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib100)). nature of their disorder renders medication risky (risk addiction/suicide)
Brain stimulation - attractive option because they are cheap, tractable, and deliverable in low socioeconomic and non-compliant populations ([Ekhtiari and Bashir, 2010](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib54)).
some hurdles when looking at these studies
* replicability,
* establishing appropriate cognitive and neural targets for tES : appetitive or impulsive motivational states , compulsive motivational states, risky decision making, executive control
* understanding tES-induced [neuroplasticity](https://www.sciencedirect.com/topics/neuroscience/neuroplasticity) with patients under the influence of drugs. Neuroplasticity changes during tES = affected by the type of drug of abuse, level of dependence, and duration of abstinence ([Grundey et al., 2012](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib62))
* inter-individual differences - neurocognitive variances within drug-dependent populations
110
tES: Public Communication of Results
* over-exaggerated claims for other domains = whatever e.g., the discovery of grid cells ([Moser et al., 2008](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib88), [Moser et al., 2014](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib89))
* The difference with tES is that overblown and unreplicated claims that tES can improve language skills - leads n either demanding tES or trying it out for themselves
* The responsibility here lies entirely with the scientists
* When it is claimed that tDCS can improve problem-solving abilities ([Chi and Snyder, 2012](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib34)), the casual reader will not notice that only one-third of subjects improved, that there is no evidence that effects are sustained beyond 3 min, that there was no active control stimulation, and that there was no control for order effects.
speculations based on what has not been done
* suggestions that tDCS may have uses in the military ([Levasseur-Moreau et al., 2013](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib80)) or in sport ([Davis, 2013](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib42)).
* Tno evidence that tDCS can even produce its classic excitatory or inhibitory effects in M1 in subjects who are moving during the application of the stimulation
* nor that in any significant, replicated effect, the stimulation can benefit subjects beyond a few minutes.
111
tES: Public Communication of Results, voices of reason
* [Sehm and Ragert (2013)](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib124) have articulated very well the limitations of tES in the military: third party effects, unknown long-term dangers, the problems of transferring effects to the real world, and the specificity of modulation
* [Davis (2014)](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib43) also makes a strong case for caution. He focuses on the unknown effects of stimulation, the unknown side effects of stimulation (an important distinction from the first), the lack of clear dosing guidelines, and the lack of translational studies from adults to children. The extension to children is disturbing
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Accounts of the need for regulation of tES have appeared recently
Some studies (e.g., [Andrade et al., 2013](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib4)) have stimulated children as young as 5 years old before any significant modeling data or even safety predictions are available - dangerous as such studies being taken as precedents for safety.
* [Santarnecchi et al. (2013)](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib123) have argued for the need to regulate the use of devices. In a counter,
* [Walsh (2013)](https://www.sciencedirect.com/science/article/pii/S0896627315006741#bib155) has noted that regulation of such simple devices in this technological age is next to impossible, and that if the brain stimulation scientists can instead regulate their language and hype, this may not even be necessary.
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