tDCS course Chapter 3 Mechanisms of tDCS - #22 - May 24, 2025

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Welcome to the Neurostimulation podcast.

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I'm Dr.

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Michael Passmore, clinical associate

professor in the Department of

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Psychiatry at the University of

British Columbia in Vancouver, Canada.

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The Neurostimulation podcast is

about exploring the fascinating

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world of neuroscience and clinical

neurostimulation in particular.

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Every week we have interesting

conversations with leaders in the field.

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We have conversations with experts

in general health and wellness, and

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from time to time, we focus in on

research studies and information that

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is included in important textbooks in

the area of clinical neurostimulation.

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In today's episode, we're going to

continue in our exploration of the

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textbook called Practical Guide to

Transcranial Direct Current Stimulation.

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It is going to be another exciting

exploration into the fascinating

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mechanisms behind tDCS, what's

really happening inside the brain

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when we deliver that tiny current.

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Stay tuned to find out.

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So tDCS or transcranial Direct Current

stimulation is a non-invasive brain

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stimulation technique that delivers a low

level electrical current to targeted brain

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regions through electrodes on the scalp.

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While the method is deceptively simple,

typically involving only one to two

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milliamperes of direct electrical

current, the science behind its effects

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on brain function is anything but basic.

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So why care about it?

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Because tDCS has been shown to modulate

mood, cognition, motor performance,

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and can even enhance recovery from

certain neurological conditions.

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But understanding its full potential

hinges on knowing the biological

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mechanisms that underlie both its

acute effects, those that occur during

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and shortly after stimulation, and

the after effects, which may last for

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hours or even days to weeks afterwards.

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Let's start with some fundamentals.

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So when tDCS is applied, it seems to

alter the transmembrane potential of

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neurons in a polarity-dependent way.

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Anodal stimulation, the positive

electrode, generally depolarizes neurons

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bringing them closer to firing, whereas

cathodal stimulation, the negative

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polarity, tends to hyperpolarize

neurons making them less likely to fire.

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But it's not always that simple.

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The direction of current flow, the

neuronal orientation and the pattern of

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cortical folding of the outer part, the

cortex of the brain, all play a role.

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Neurons that are aligned in

parallel to the electrical field

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will be affected differently than

those aligned in a perpendicular

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fashion to the electrical field.

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This is why brain modeling is crucial

to understanding individual responses.

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What about the acute effects?

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This appears to be more than

just influencing neuronal

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firing rates during stimulation.

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tDCS can change a number of things.

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First is the spontaneous

neuronal activity.

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Second is the responsiveness of

neurons to sensory input, and third

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is the firing thresholds of neurons.

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For example, studies using single cell

recordings of neurons in animal studies

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and in brain slice preparations have shown

that direct current fields as small as one

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volt per meter can significantly modulate

neuronal excitability with without

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triggering action potentials themselves.

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This mechanism is known as this mechanism

is known as sub-threshold modulation,

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meaning that neurons are kind of nudged

toward or away from firing, depending

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on the current that's being applied.

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This type of modulation can shift

the balance of excitatory and

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inhibitory signaling, which might

explain why tDCS can reduce symptoms

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in depression or enhance learning in

applications to target cognitive issues.

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Now let's look at the after effects.

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What might we be able to say about

lasting change through neuroplasticity?

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One of the most intriguing aspects

of tDCS is the after effect, even

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after the current is turned off,

neural changes appear to persist.

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Why is that?

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The answer lies in neuroplasticity.

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Key mechanisms appear to include long-term

potentiation, which is important for

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memory formation, as well as long-term

depression like processes, modulation

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of NMDA receptor activity, particularly

under anodal tDCS, involvement of voltage

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gated calcium channels, especially

of the L type and signaling of brain

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derived neurotrophic factor or BDNF.

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Animal studies have shown that

tDCS can modulate gene expression

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and alter synaptic strength.

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And these changes are thought

to underlie learning and memory.

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And they're why tDCS is being used

in areas like stroke rehabilitation,

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and cognitive enhancement research.

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Now, let's consider beyond neurons and

look at some of the important aspects of

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the micro architecture of brain tissue.

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Things like glial cells, the vasculature,

and how that all fits together to

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produce the network effects in the brain.

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Recent research has moved beyond a neuron

only model in terms of the effect of tDCS.

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It is increasingly recognized

that tDCS may also affect.

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Cells like astrocytes, which regulate

the neurotransmitter uptake and ion

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balance, microglia, which potentially

involves an alteration of inflammation

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or neuroprotective mechanisms and

endothelial cells in the vasculature

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of the brain, which influence things

like neurovascular coupling, cerebral

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blood flow, and the blood brain barrier.

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Then there are these

network level effects.

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So tDCS appears to be able to modulate

things like functional connectivity,

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not just at the stimulation site, but

also across resting state networks

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like the default mode network

or executive control networks.

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So this could explain how targeting

the dorsal lateral prefrontal cortex or

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D-L-P-F-C, in particular with tDCS can

improve things like working memory or

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alleviate depressive symptoms in part

by modulating broader brain circuits.

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Now let's consider the complexity

and the importance of personalized

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treatment in order to address

individual differences in the clinic.

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tDCS is not a one size fits all.

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Treatment variability arises due to

factors like skull and scalp thickness

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from person to person, cortical folding,

and subtle differences in brain anatomy,

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as well as neurotransmitter system

differences, and the ongoing brain

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state at the time of stimulation.

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These factors are why computational

modeling and personalized dosing are

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increasingly recognized as very important.

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The new research emerging on high

definition tDCS or HD-tDCS and MRI

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guided targeting is aiming to improve

the vocality and reliability of

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outcomes so that the treatment can be

delivered in a more personalized manner.

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So what are the clinical implications

and some directions for future research?

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Well, understanding all of these

mechanisms isn't just academic.

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It's highly relevant to clinical practice.

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If we know how tDCS alters neuronal

excitability and neuroplasticity,

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we can do a few things.

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First is fine tune treatment protocols

for specific conditions like depression,

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stroke, or chronic pain conditions.

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Second is combine tDCS with

things like cognitive training or

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physiotherapy for synergistic effects.

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Third is to design better devices that

optimize current delivery based on

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individual anatomy and clinical needs.

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Yet, there are still questions

such as, what's the best dose for a

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given condition, how do we predict

responders versus non-responders,

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and can we make tDCS more consistent

in terms of effectiveness and

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tolerability across individuals?

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It's clear that tDCS is a powerful

neuromodulation tool with both promise

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and complexity, so by continuing to

uncover its underlying mechanisms,

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from cellular polarization to synaptic

plasticity and network dynamics, we're

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moving closer to harnessing its full

potential in both the clinic and the lab.

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Thanks again for joining me on this

deep dive into the science of tDCS.

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If you enjoyed today's episode, don't

forget to like and subscribe, leave a

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comment or a question or a review in

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to share this with a colleague or a

family member or a friend, really anyone

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that you think might be interested in

neuroscience or clinical neurostimulation.

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Thanks again for joining me on the

Neurostimulation podcast today.

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I really appreciate your interest,

your time, and your attention.

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Tune in next time where we

explore another interesting topic

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in the world of neuroscience

and clinical neurostimulation.

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Until next time, be well and stay curious.