“Transcranial direct current stimulation (tDCS) – A general purpose

neuromodulator?”Dan Ofer.

Hebrew University of Jerusalem.

ddofer@gmail.com

21.9.2013

Introduction:

The goal of this paper is to present transcranial direct current stimulation (tDCS)

and to argue that it is a general modulator of neuronal excitability and plasticity, as

evidenced by the extremely diverse mental functions and neuroanatomical regions

affected by tDCS in varied studies. This, as opposed to being specific to only a single

domain, cortical network, region or mental function. Towards this argument, I shall

present a wide array of different cortical regions and effects modulated in tDCS

experiments.

‘What is tDCS?’

Transcranial direct current stimulation (tDCS) is a form of non-invasive external

electric stimulation of the cortex. It works via a weak electrical current (typically 0.5-2

mA) passed between electrodes attached to the scalp, polarizing the underlying brain’s

cortex tissue with an electrical field.

(The following wording is adapted from reviews1–4): "tDCS can modulate

cortical excitability and spontaneous firing activities in the stimulated region by shifting

the resting membrane potential, thus altering the ‘intrinsic’ neuronal excitability.

Depending on the polarity of the current flow, cortical excitability can be increased via

anodal stimulation or decreased via cathodal stimulation. "

tDCS induces cortical and neural plasticity via subthreshold polarization of the neuronal

membrane via weak direct electrical currents and induced electric fields.5–7

tDCS’s Physical Basis - “What it Does”:

In terms of its relationship to neuroelectric activity, tDCS is a neuromodulator –

it alters excitability, increasing or decreasing the threshold of excitation and thus the

firing rate and activity of affected neurons. However, it does not cause neurons to fire

"independently"; that is, it modulates existing activity but does not induce

“independent” firing. In contrast, in TMS (Transcranial Magnetic Stimulation) or

electric shocks 40, “resting” or non-active neurons are induced to fire, independently of

“natural” activity because (static) electrical fields in this range do not yield the rapid

depolarization required to produce action potentials in neural membranes 2. The effects

of tDCS on cortical excitability can last for a varying amount of time8, depending on the

region affected, the function involved, and the strength and duration of the tDCS

stimulus itself.

Hence, tDCS is a neuromodulatory intervention. The tissue is polarized9 and

tDCS modifies spontaneous neuronal excitability and activity by depolarization or

hyperpolarization of the resting membrane potential (Vmr)”.

The extent of tDCS's effect depends on a number of factors2:

i. Current density (dependent on current strength and the size of the electrode).

This determines the strength of the induced electrical fields. It has been shown that

higher current densities result in stronger effects10–14.

ii. Duration - Longer stimulus' durations (all other factors being equal) determine

the occurrence and duration of effects in humans and animals2,14–20. It should be noted

that there can be significant differences in effects in cases where tDCS ‘treatments’ are

spaced out at intervals, rather than a single exposure2,3,20–23. Multiple spaced exposures

tend to have longer lasting and more potent effects than a single exposure 3,24. However,

the mechanisms underlying these changes are not well understood, as is any possible

relation to long term potentiation [LTP].25,26 It is currently unknown whether using

spaced intervals would result in greater (or longer lasting) effects for other studied

phenomena. The exact underlying differences between effects that last for days, weeks,

months or hours are as yet unknown.

iii. Orientation of the induced electric field set by the electrodes’ positions and

polarity (Anodal or Cathodal stimulation). The positioning determines the areas of the

cortex affected by the current flow and the induced electric field, while the polarity

determines the effect (increased or decreased excitability due to ‘depolarization’ or

‘hyperpolarization’ respectively).

(3:)“Early studies in animals15,27 […] using direct cortical stimulation showed

that if the anode was placed above or within the cortex, spontaneous neuronal activity

was increased, whereas cathodal polarity resulted in reduced spontaneous unit

discharges due to subthreshold changes in membrane polarization. […] However,

neurons throughout the cortex were not modulated in a homogenous manner. […]

different subpopulations of neurons appear to have different thresholds for

modulation.27”

It must be noted that the mechanisms underlying the changes in cortical

excitability induced by tDCS are different for those effects seen during stimulation and

those induced after the stimulation has stopped 3 – meaning, that there are differences in

the physiological effects and underlying facilitating mechanisms involved, depending on

the timeframe i.e. - during or after the tDCS stimulation.

“Effect of tDCS on Neurons during Stimulation: ∆Vmembrane”

(3:)“The effects of anodal {= increased excitability9} tDCS during stimulation

appear to be solely dependent on {depolarizatory} changes in membrane potential”. This

was established by Nitsche et al6, using pharmacological methods (flunarizine and

carbamezipine) that blocked calcium 105 (Ca2) or sodium (Na+) channels, reducing or

abolishing (respectively) the effects of anodal stimulation for the treated neurons. 9

During cathodal stimulation, the reduction in excitability caused is seemingly

unhindered6 by calcium or sodium channel blockers, as would be expected3 if the

neuron’s membrane is indeed hyperpolarized by the cathodal tDCS.

NMDA and GABA receptor antagonists had no effect on the ‘immediate’ effects

of either anodal or cathodal tDCS, as would be expected from a shift in Vmembrane/the

resting membrane potential (as opposed to an effect exclusively dependent on synaptic

plasticity) 26,3,6,7

“After-effects of tDCS on Neurons post Stimulation:

The mechanisms involved in tDCS effects lasting after the stimulation has passed are

more complicated and less understood. Generally speaking, the effects of a single tDCS

stimulation can last for hours18,28 or longer, in the case of multiple ‘spaced’ treatments,

with some cognitive effects seen to persist for days or weeks after. 13,22,29–32

It seems that the long term effects are the result of GABAergic (for anodal tDCS1) and/or

glutamergic (ex: NMDA receptors) modulation, with a major component in lasting effects

being synaptic plasticity and interneurons.1,3,5,6,8,9,22.

It also appears that tDCS promotes changes in levels of brain-derived neurotrophic factor

(BDNF), an important element for neuronal proliferation and survival. 1, 100

To summarize, these match what might be expected from a neuromodulator, with

immediate stimulation causing a moderate shift in the neuron's membrane potential

(hyperpolarization or depolarization, depending on the polarity), but said ∆Vmembrane shift

is not sufficient in itself to induce neurons to fire spontaneously, or to prevent their

activity altogether.

However, it does affect the critical threshold of ‘input’ from external stimuli required in

order for the neuron to fire an action potential. In the ‘long run’, we would indeed expect

any lasting effects to be similar to those seen in ‘normal’ long term changes in plasticity,

but “accelerated” due to the facilitation of activity and thus excitability. We might as well

postulate as an extension of Hebb’s law that “Neurons that fire together wire together" 33,

that increased/”accelerated” or decreased firing of the functionally related neurons found

together in a network or region, would likely lead to an increase or decrease respectively

in the strength of the relevant intersynaptic and/or intra-network connections at a faster

rate than the baseline, possibly via theorized LTP/LTD like mechanisms1,26,34,,

“strengthening the neuronal synaptic connections and making them more efficacious”35

tDCS as a Research Tool

Recent years have seen tDCS reintroduced (study of the effects of electricity on

the brain is quite ancient) as a noninvasive research tool for altering neuroplasticity,

modulation of cortical function, neurorehabilitation, and in linking between behaviors &

mental functions to varied regions of the brain 65.

Its exponentially increasing popularity in recent years 92 is derived from a

number of characteristics 2: 1. Rapid effect. 2. Exact neuroanatomical targeting (as

opposed to pharmacological means), albeit at a relatively “coarse” scale. 3. Cheap. 4.

Relatively easy to use and safe. 5. Noninvasive and can be used in conjunction with

other tasks. 6. Flexibility – can be used to investigate an extremely large variety of brain

regions, behaviors and mental functions. 7. Potential uses in healthy subjects.

5,10,12,13,17,19,21–24,26,29–32,46,47,57,58,66,67,70,77,78,81,86,87,89,91,92 . 8. Ability to serve as a tool for linking

neuroanatomical regions to behavioral functions.37

See Figure 1, supplementary material.

tDCS Effects on Mental Functions:

As mentioned in prior reviews, tDCS has been shown to have an effect on a very wide

range of mental functions and behaviors 1,2,3. In the following section, I shall present a

sampling of different effects, covering different behavioral and cognitive functions,

achieved using tDCS stimulation (anodal or cathodal, depending on the specifics) on

different neuroanatomical regions in humans, or different effects seen from stimulating

the same regions of the brain (in other studies which stimulated that region).

To reiterate, the overall goal of this paper is to argue that tDCS is a general

mental neuromodulator (via its modulation of neuronal excitability), rather than

being a “domain specific” effect 36 limited to only a single ‘modular’ a mental

function.

The majority of tDCS experiments focusedb on the prefrontal cortexc (PFC), the

dorsolateral prefrontal cortex region (dlPFC) and the motor cortexd, particularly the

a http://www.cognitiveatlas.org/concept/domain_specificity36

b Source: Probable association by Brainscanr, and overview of the review article, in particular 2.

http://www.brainscanr.com/Search?term_a=TDCSc This often includes, roughly speaking, the prefrontal (anterior and rostral) cortex itself (PFC),

the Orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (dlPFC).

primary motor cortex (M1). A number of other regions are also examined, in particular

the primary somatosensory cortex (S1) and visual cortex. 2

While most of the studies presented here focus on the effects on functions evoked

by tDCS, it must be noted that a major and growing use of tDCS is to infer the

involvement of neural regions in varied functions, such as for example; the role of the

cerebellum in verbal working memory37, or suppression of the non-dominant hand's

motor cortex by the M1 region controlling the dominant hand38,39. In the aforementioned

cases, this was investigated via inhibitory/cathodal tDCS on those regions in conjunction

with tasks involving the functions studied. Furthermore, in these studies, impairment of a

function following modulation of a neuroanatomical area, typically in the form of

cathodal tDCS "inhibition", is used as supporting evidence towards the hypothesis that it

does indeed play a role in the affected function, whether directly or indirectly.

The inclusion of a number of cortical structures and associated effects was

inspired by both articles2,3,24,26,40, and the brainSCANr engine (“Brain Systems,

Connections, Associations, and Network Relationships”).

http://www.brainscanr.com/Search?term_a=TDCS. 41

See Figure 2 & 3, supplementary material.

Motor Cortex Studies:

tDCS studies involving the motor cortex have shown potentially beneficial effects which

can be attained using tDCS even in healthy individuals42. The primary motor cortex (M1)

d This includes the primary motor cortex (M1), the premotor cortex, and supplementary

motor cortex

is a popular target in studies involving motor learning due to its suspected role in the

initial ‘encoding’ of motor skills (‘initial formation of memory’)43, 24, the relative ease of

quantifying results, and its being one of the earliest most studied areas in the field14,27,44.

M1 modulation may also affect other areas such as the premotor cortex 24,45,46. In addition,

there is a distinction24 between learning new motor skills and improving performance of

existing motor skills'.10,24,42,47 Review and meta-analysis studies have shown that anodal

tDCS increased corticomotor excitability.10,24

In regards to (lasting) effects; “tDCS produces lasting effects in the human motor cortex.

These are stable for up to about an hour if tDCS is applied for 9-13 minutes. Anodal

stimulation enhances, whereas cathodal tDCS diminishes excitability, as measured by

motor-evoked potential (MEP) amplitude”2,18

Hand Motor Performance: A study of non-dominant hand motor performance and

control48, as measured with the Jebsen Taylor Hand Function Test (JTT), reported the

following:

Anodal (excitatory) tDCS stimulation of theM1 contralateral to the non-dominant hand,

(= the Left hemisphere, for the right handed subjects), resulted in “significant

enhancement of JTT performance after 1mA anodal tDCS of M1 (mean improvement of

9.41%), but not after sham” 48. The study reported improvement in the non-dominant

hand, but not the dominant hand. This seeming contradiction with other studies reporting

‘all-around’ improvement is explained by the fact that the JTT task examines motor

performance and control, rather than motor learning. As the author notes, the non-

dominant hand’s “governing” motor cortex region is characterized by having a higher

motor threshold and lower motor evoked potential [MEP], as a corollary to its relatively

lower intrinsic excitability48,49 compared to the dominant hand’s motor cortex.

Motor Learning: A number of studies have shown tDCS evoked enhancement of

motor learning, in both healthy and sick individuals. Reported results vary due to the

differences between tasks, the complexity of the tasks and stages of learning studied 24, as

well as possible methodological inconsistencies1,2 (for example, differences in: electrode

montage placement and electrical field orientation, stimulation duration, and current

strength).

Still, a number of studies16,24,26,38,39,42–46,48,50–53 have shown improvements in motor

learning and/or rehabilitation with tDCS stimulation. A typical example is a study of non-

dominant hand motor function enhancement via (unilateral) anodal stimulation of the

contralateral motor cortex 24,44,51, or/and47,53 inhibition of the ‘opposing’ hemisphere’s

motor cortex via cathodal stimulation.38

The wide range of effects, most of which showed “improvements” (as measured

by varying criteria) include better results in recovering motor skills among stroke

patients10,47,50,54, enhanced retention of motor skills, 44,51 , the previously mentioned

effects24 on (non-dominant) hand motor skills' performance 38,39,48,54, implicit motor-

sequence learning24,44,35, modulation of long term motor memory, implicit and procedural

skills learning, retention and consolidation 3,55,104, explicit sequence learning (in a bilateral

stimulation experiment) 53, increased “practice-dependent plasticity” i.e. magnitude and

duration of newly acquired motor memories51 and visuomotor tracking/coordination task

performance following a-tDCS stimulation of the contralateral M1 or extrastriate visual

cortex area MT+/V5 (but not of the primary visual cortex) 52

Motor Studies Discussion:

To summarize, the overall consensus 42, 20 would seem to be that “tDCS {is} […]

capable of inducing lasting improvements in motor function. […and] has shown

preliminary success in improving motor performance and motor learning in healthy

individuals, and restitution of motor deficits in stroke patients.”42

An aspect worthy of reemphasis is the two types of functional enhancements seen

in the aforementioned studies (and the following section):

(1) Immediate ‘performance’ enhancement; for example, increased dexterity and

control in the JTT test48 (these effects are seen in tasks where tDCS improves

performance, even without training56)

(2) ‘Faster/enhanced’ learning and/or plasticity, as seen in memory retention and

formation44,51, reconstruction of (motor) skills in stroke patients10,10,47,50,54,57, or effects seen

when tDCS is applied during training24,46,58.

The connection or causation between these two ‘effects', if there is one, is

unclear20,24,28, and requires further study beyond the scope of this work. While it might

seem likely that a positive link exists, evidence is currently sparse, with some negative

examples showing a negative correlation between the learning slope, reaction time and/or

accuracy or control26, 44.

In addition, some effects or changes might be network specific, or due to

stimulation of ‘competing’ or inhibiting neighboring regions, thus impacting various

performance criteria for some tasks, but not others. For example, cathodal stimulation of

the opposing hemisphere-motor cortex region, rather than anodal stimulation of the

contralateral M1 hand region, has a similar but not identical facilitatory effect 47,53,56,59.

Repeating previous experiments with fresh experimental paradigms may well add new

insight to this issue. These measures might include: ±Left/Right/dual hemisphere

stimulation × ±anodal × ±cathodal, larger samples, different tasks (measuring the learning

or performance rates improvements, increases above the ‘baseline’ and retention),

uniform stimulation intensity/current strength2 and improved neuroanatomical resolution

via new “high definition tDCS” techniques5 which allow stimulation of smaller, more

focused regions.

Cognitive Studies:

A great many tDCS studies on higher mental functions or cognitive effects have

focused on stimulation or suppression of the prefrontal cortex (PFC) and its connected

regions, especially the dorsolateral prefrontal cortex (dlPFC)30,60 and the orbitofrontal

cortex (OFC)61–63. Interest in these regions is primarily due to their suspected roles in the

‘highest’ mental and cognitive functions such as planning64, ‘executive functions64’,

working memory [WM]20,30,32,65–68, behavioral regulation69 and decision making62,70–72; the

most “advanced” and ‘intellectual’ mental functions that we possess as “intelligent”

beings.

A diverse array of mental functions show potential for modulation by tDCS.

Many even show ‘enhancement’ – i.e. improvement beyond the baseline in healthy

individuals. Among the best established and most documented of tDCS evoked effects is

‘improved’ WM, via anodal-tDCS [a-tDCS] stimulation of the dlPFC 26,30,32,66,67,73.

WM is the limited capacity storage system involved in the maintenance and

manipulation of information over short periods of time. WM plays a key role in a wide

rangee of higher order cognitive functions”74. WM is one of the few known

“transferable”75 elements of general or “fluid” intelligence76, with a wide array of

cognitive functions benefiting from it.74 It is typically measured using a n-back task30, and

is suspected to be malleable with training30,75,76.

Anodal {excitatory} tDCS stimulation [a-tDCS] over the dlPFC has been shown

to improve verbal and visuospatial32 working memory30,67,77, both in patients

(poststrokes24,32,54,65,75, Parkinson’s disease73 or Alzheimer’s disease78), and in

healthy30,32,66,67 or elderly12,78,79 adults. Stimulation of the left PFC is associated with verbal

WM17 and naming ability improvement, while a-tDCS of the right PFC is associated with

improving visuospatial WM. 32

Other cognitive effects:

Explicit motor learning as noted in the previous, motor section, with

dlPFC modulation was also seen to have an effect in some cases 24,78,80.

Improved retention, consolidation21,55,80 and reconsolidation23 of (verbal)

declarative memories17,21,26,77 , following unilateral-left dlPFC a-tDCS. At the same

time, M1 stimulation was not found to affect verbal memory performance77.

e Examples of WM associated functions:

http://www.brainscanr.com/Search?term_a=working+memory

Anecdotally, strongly reported positive feelings of improved focus,

clarity29, concentration29,81 and a state of “flow”82,40,83 (flow is “a state of

concentration or complete absorption with the activity at hand and the

situation.”84).

The aforementioned effects make tDCS a potential tool for ‘speeding up’

learning,2,51,58,67,77,82,83,85,29,40, in a variety of real world tasks 86.For example, training

for “complex threat detection”, found a 2.3 fold improvement in the training time

required, via improved alertness-attentional control81, following a-tDCS of the

right inferior frontal cortex during training29. The difference between the test and

‘sham’ groups was retained for over 24 hours after the training ended.

Creativity and novel-insights 87: participants who underwent cathodal

stimulation of the left anterior temporal lobe (ATL) together with anodal

stimulation of the right ATL were three times as successful at solving an

insight/creativity task (“matchstick arithmetic”) compared to a control group

(reversing the hemispherical A/C stimulation showed less of an effect, possibly

due to a “ceiling effect”, reminiscent of the aforementioned M1 hand studies).48

“Long-lasting changes in numerical competence”: in this study, healthy

adults were stimulated via tDCS while learning artificial numerical valuesf. They

were later tested for “numerical competency”. The group which had anodal and

cathodal tDCS stimulation to the right and left (respectively) parietal lobes during

training showed “better and more consistent performance in both numerical tasks”

f They were stimulated for 20 minutes at the start of the 90-120 minute learning phase. They

were not stimulated during the testing.

compared with the control group. Interestingly, six months after the experiment,

that group still showed improvement. Another group with ‘reversed’ stimulation

polarity showed reduced performance. The training derived effect was seemingly

task-specific, with performance in the tasks using normal numbers not showing

change. 22

Inhibitory control of voluntary actions was enhanced or impaired via a-

tDCS or cathodal tDCS (respectively) to the pre-supplementary motor area. 106

Verbal & Lingual abilities: in addition to the aforementioned effects of left dlPFC a-

tDCS on verbal working memory, other studies have shown that:

o A-tDCS over the right temporal-parietal cortex combined with language

training significantly improved naming ability in patients suffering from chronic

anomic aphasia (severe problem with recalling words or names)88.

o a-tDCS of the left posterior perisylvian region (included Wernicke's area)

in healthy subjects, during a “visual picture naming task” also showed

significantly faster and equally accurate naming responses following

stimulation.89

o Cathodal tDCS over the Cerebellum impairs verbal working memory37,

implying cerebellar involvement in the function (excitatory/a-tDCS was not

tested).

o dlPFC a-tDCS affects “long term” verbal memory consolidation17 (initial

memorization) and reconsolidation23,23 (renewed consolidation/storing of a

memory following its retrieval), with both showing ‘enhancement’ i.e. Improved

speed and recognition accuracy when tested on verbal memories17.

o A-tDCS over Broca’s area was shown to enhance “implicit learning of an

artificial grammar”. 90 The effects were seen to be specific to rule-based

knowledge of the artificial grammar and detection of “syntactic violations” and

were not the result of differences in W M.

A-tDCS stimulation of the auditory cortex was found to improve the

abilities of healthy subjects in “temporal auditory processing abilities”, as

measured by the subjects’ ability to discern auditory temporal resolution. Cathodal

tDCS reduced performance compared to the control group.91

tDCS experiments with aged, healthy subjects have shown “reversal” of some age-

related impairments in mental abilities to a more ‘youthful’12 state92. Known effects

include:

Right temporoparietal cortex stimulating leading to improved object-location learning

(learning the positions of buildings on a street map), with improved recall lasting for at

least one week93. M1 stimulation affecting acquisition of complex motor skills, lasting for

over 24 hours 94. Age related hyperactivity in a number of neural networks involved in

semantic word generationg was notably ‘reduced’ with improved task performance,

following a-tDCS of the left inferior frontal gyrus.12

g This included the PFC and anterior cingulate gyrus

Other age related declines have been noted to be ‘alleviated’ by tDCS in studies

focusing on patients suffering from Alzheimer’s disease (for example, object

recognition).78,92

Additional Behavioral Effects:

Cathodal tDCS over M195 or primary somatosensory cortex (S1) has been

shown to reduce induced pain sensations/nociception. 96

dlPFC tDCS stimulation has also been found to reduce ‘craving’ for

specific foods97 and alcohol98, to alter probabilistic thinking 68, probabilistic

forecasting (switching between frequency matching and expectancy maximization

strategies70) and risk-taking ('risk-appetite') behavior71,72.

Polarization of the visual or parietal cortexes modulates the threshold for

motion or tactile perception, respectively (i.e – increased or reduced sensitivity).

101-103

tDCS applied during slow wave sleep affects verbal declarative memory,

improving retention of 'word pairs'21, and also facilitates "sleep dependent

consolidation" of procedural motor memories – enhancing retention

(consolidation) of these none-declarative memories 94,92. Different sleep frequency

bands were also affected 21.

Discussion

tDCS has a number of different modulatory effects on various mental, cognitive,

behavioral and neurobiological processes.. It is capable of inducing modulatory changes

in many different systems, and neural regions 1. tDCS induced physiological changes may

result in both local and distant changes in excitability, inhibition and potentially changes

in plasticity (local or synaptic).

The effects underlying the immediate or lasting effects involved in tDCS, and the

changes derived from and affected by it cannot be simplified narrowed down to only one

basic mechanism such as ’reduced dopamine reuptake‘ or ’spontaneous motor activity

induced by strong electrical shocks of the motor nerves‘.

As has been noted here previously, effects differ in regards to:

i) The mental, behavioral or cognitive functions affected. Effects modulated

include declarative memory 21,77, motor performance and control 38,39,48,

consolidation 55,104 and reconsolidation 23,24 of memories, attentional

control 56,81, visual and tactile-sensory perception and sensitivity 56,101,103,

visuomotor tracking 52,101, working memory 30,32,37,66,67, risk appetite

behavior 70-72, cravings 97,98, creativity 87, planning ability19 , language and

artificial grammar rule-learning90-92, and the many other effects previously

listed in both this text and existing literature 1-3,92.

ii) The cortical area(s) affected:1-3. Stimulation of different regions of the

brain can affect the same functions and/or different functions, depending

on the areas, their roles and the functional network involved in a function.

Given examples include: WM modulation via the cerebellum 25,37 or

dlPFC, and involvement of both M1 and the PFC in implicit learning of

motor skills 20,30,35,39,42,45,48,51. This as opposed to tasks found to be

unaffected by stimulation of one of the ‘generally involved’ areas (V1,

M1, dlPFC in the case of motor related tasks), in cases such as task-

specific differential effects on task switching performance 46 or visuomotor

tracking 52,101.

iii) While most investigated functions can be impaired, usually but not

exclusively, by cathodal tDCS, far fewer functions can be “enhanced”. For

example, dominant hand motor performance in healthy individuals, (at

least in existing studies) 48.

That said, a large number of effects show enhancement in healthy

adults10,19,24,38,67,68,70,87,89 or improved restoration (sometimes when combined with training

74,88) towards healthy or normal levels in the case of the elderly 92-94, post-stroke patients

47,50,54,65,and Alzheimer's or Parkinson's disease's patients 73,78.

These effects typically involve: A) broad, trainable ("training dependent plasticity" =

interactions between training with or without tDCS) mental functions such as WM 74-76 or

other effects of ‘executive planning' and so called 'higher mental functions' 56,58,80-87.

B) The other type that seems most 'amenable' to 'enhancement' are functions controlled

by regions which have deteriorated and have reduced plasticity or excitability. Examples

include age related decline in cognition and mental capabilities. tDCS has been shown

temporary reversal of many of the aforementioned age related symptoms or connectional

characteristics 12,92-94 and enhancement of motor control and performance in the non-

dominant hand38 (which is theorized to be 'suppressed' by the dominant hand 49). In all

these cases, the tDCS "resets" excitability towards what is likely the 'healthy baseline'.

What exactly determines if a function can be enhanced, with or without training

or enhanced in a lasting, training dependent or independent fashion29,40,56,58,83, is beyond

the scope of this work, save for speculation.

i) The duration of effects after the stimulation has ended can vary

immensely, both in regard to the post-immediate effects following the end

of the stimulation (typically occurring over hours 14,15,18,34), and in regards

to the duration of the functional changeswhich can persist for days 29 or

even months! 19,22 Multiple mechanisms are possibly involved in such long

lasting effects, likely including (but not necessarily identical to) neural

and/or synaptic plasticity 1,28,100 + LTP and/or LTD like effects 1-3,6,7,27,28,

modulation of GABA, Glutamate and/or NMDA receptors1,6,7,13,105,106-108,

involvement of regulation/effects from related neural networks 1,3,107 and

regulatory factors, such as BDNF 100.

ii) The numerous cases of left/right specificity of effects, not just for motor

effects 39,42,53 but also for abstract mental functions (such as declarative

verbal memory77 or working memory67) is somewhat peculiar. Perhapsthis

might prove to be an artifact of current leakage affecting surrounding

structures or shared inhibitory interneuronal networks, with bilateral a-

tDCS+ cathodal tDCS inadvertently focusing the effects to sub-structures.

Claims of tDCS being domain specific or a modulator of only a single effect

appear invalid, given the numerous listed examples of different effects for different

regions, and the wide range of effects.

Modulation of WM and attention could possibly have an influence on a number of

the effects 60,74,76 and possibly even some of the behavioral effects, such as reduced risk

appetite behavior being a consequence of improved probabilistic thought/numerical

competency, and that being somehow derived from a boost to WM – but it still fails to

explain all the dlPFC related effects (cravings97,98 for example), and completely fails at

explaining effects evoked from stimulation of regions remote from the PFC. Still, the

possibility of WM as an underlying 'cause' behind many known cognitive and behavioral

effects seen as a result of imprecise/"conventional"5 tDCS currents applied to the dlPFC

'leaking' is an interesting one, and could easily be investigated as a confounding effect via

testing for changes in WM using an n-back test, and examining the r-Pearson's correlation

for WM changes relative to whichever effects are being primarily examined.

The possibilities for further research are vast. A number of interesting questions

include: what other cognitive effects show lasting changes (relative to a control group)

for weeks or months following tDCS stimulation? Are any such effects training

independent (all given examples of long lasting effects have involved training88, albeit

with differential effects seen for novices in some cases 86)? Can effects from different

brain regions or networks "overlap" in an additive manner? (For example, this is

examinable via simultaneous a-tDCS of the dlPFC and other areas known to be involved

in a task, and comparison of results to see if interaction or additive effect(s?) exist).

Stimulation of novel areas and investigation at higher resolutions for which regions

within structures are involved in modulation of functions associated with the entire region

(sub-regions of the dlPFC and WM for example).

The potential "real world" uses are known, in particular for rehabilitation 2,16,50,65,

but the potential use as a so called "thinking cap"87 for healthy individuals is even more

exciting. Studies have already taken place in the real world with healthy individuals 29,40,81,82,83, but more are needed to help establish the generalizability of the potential

effects, to help establish the safety of long term use 2,11 and optimize parameters for such

usage (in terms of electrode orientation and location, current intensity and 'side-effects' 99). Two interesting ways to test this, with a large study group of healthy adults, would be

to try the following: i) A study of the effects of a-tDCS on language learning; given

stimulation of a combination (requiring an additional 'additive' experiment to establish

the most effective combination) of Broca's area, Wernicke's area and/or the dlPFC. This

could be applied in conjunction with an existing language course, or even a

code/programming language course. ii) Another idea is a-tDCS of the dlPFC, and/or the

anterior temporal lobes ("insight facilitation"87) with volunteers in an academic

environment, such as a theoretical training course or academic class, applied at the

midpoint of a course, so as to observe the effects on learning 40,82,83. Given such a large

group (even a sub-section of volunteers from one), any effects in grades or improvements

for the non-sham group can be easily compared to the rest of the class, and their own

previous performance.

This would be an excellent way to test applicability and potentially enhancing effects

with a large group of healthy subjects, and would not be overly expensive given the

relative simplicity and compactness of a basic tDCS kit. This would help in testing the

effects in challenging, noisy environments with a focus on uses that would have far

reaching implications for healthy people, while the large test groups would help in

establishing effects, as opposed to the large number of existing experiments with their

small sample sizes, a fact that makes rigorously testing something with multiple A/B/C

combinations statistically problematic. This could have obvious benefits 87 for

‘consumers’, with the added benefit of massively expanding the data available for use in

future rehabilitative or restorative92 studies, as well as other studies in the field, such as

examining neuroanatomical networks or the long term effects (and side-effects99).

Conclusion

tDCS modulates neural excitability1,2,6, increasing calcium levels at site of anodal

stimulation 5,7,92, altering the 'resting' electrical potential of neurons' membranes 1,3,14,27 ,

and possibly changing neuroplasticity and/or synaptic plasticity via inducing LTP or LTD

like changes6,34,38. Anodal tDCS creates an electric field, inducing a slight depolarization,

increasing the intrinsic excitability of neurons while cathodal tDCS decreases neuronal

excitability due to hyperpolarization. The after-effects of both anodal and cathodal tDCS

are influenced by glutamatergic receptors 1,3,6,7, and a-tDCS is influenced by "GABAergic

neurotransmission via interneurons" 92,106.

tDCS has been shown to affect a heterogonous array of different mental, behavioral,

cognitive and neurobiological functions. The mental and behavioral effects of tDCS

depend on the stimulation's parameters, cortical region(s) stimulated, the mental function

itself, and possible interactions with other factors, such as damage (in the case of

strokes), or decline (in the case of age related decline). Not all effects can be "enhanced"

beyond baseline abilities, and not all such effects (whether "enhancing" or "inhibitory")

are retained after the stimulation has ceased, though some tDCS-evoked effects may

persist for months. Some capabilities are "enhanced" (during stimulation) via increased

intrinsic excitability, while others benefit from cathodal tDCS reducing "noise"30.

tDCS should not be regarded as affecting only a single effect, function or region,

but rather as a general purpose neuromodulator that has different effect depending on the

variables at play, in particular the region of the brain stimulated, the polarity of the

induced electrical field, the mental or behavioral function involved and the time-period of

the stimulation.

I wish to thank everyone who helped with this paper, in particular my friends and

family, and my academic advisor.

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Supplementary Material

Fig.1 :

Source: (92) Voytek, B., & Gazzaley, A. (2013). Stimulating the aging brain. Annals of neurology, 73(1), 1–3. doi:10.1002/ana.23790

Fig 2: tDCS & TMS associations:

Source: 41 - http://www.brainscanr.com/Search?term_a=tDCS

Fig 3:

Source: 41 - http://www.brainscanr.com/Search?term_a=working+memory