tDCS course Chapter 5 Neurophysiology of tDCS - #27 - June 28, 2025

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Welcome back to the Neurostimulation Podcast.

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I'm Michael Passmore, clinical

associate professor in the Department

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of Psychiatry at the University of

British Columbia in Vancouver, Canada.

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In the Neurostimulation Podcast, we

have discussions with clinicians and

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researchers in the field of clinical

neurostimulation, neuroscience,

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and general health and wellness.

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We also explore research

articles and textbook chapters.

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And today we're going to continue our

exploration of the textbook called

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Practical Guide to Transcranial

Direct Current Stimulation.

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This is a foundational reference for

clinicians and researchers alike.

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Today we're going to talk about

chapter five Transcranial Direct

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Current Stimulation, modulation

of neurophysiological functional

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outcomes, neurophysiological

principles and rationale.

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This textbook chapter talks

about measuring change, and it

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explores how tDCS shapes brain

function through neurophysiology.

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In today's episode, we're going to take

a deep dive into how transcranial direct

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current stimulation or tDCS actually

changes brain function as revealed through

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neurophysiology and functional imaging.

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We're going to explore what's

happening at the neuron network and

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behavioral level and why this matters

for both researchers and clinicians.

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First of all, why measure

neurophysiological outcomes?

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The big question isn't just

whether tDCS works, it's how.

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So to answer that, we need

physiological measures.

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These allow us to quantify how

stimulation affects brain function,

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improve stimulation targeting and

parameters, and understand how

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brain plasticity is shaped and how

can it be modulated non-invasively.

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From evoked potentials to functional

MRI, modern neuroscience gives us

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the tools to peek under the hood and

see what's changing in real time.

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So what are the tools of the trade?

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Let's run through the main methods

used to measure tDCS induced

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neurophysiological changes.

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The first is TMS evoked motor potentials,

or MEPs, especially over the motor cortex.

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The second is EEG and event

related potentials or ERPS

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for high temporal resolution.

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The third is fMRI, functional MRI,

imaging and PET positron emission

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tomography imaging to capture

network and metabolic changes.

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The next is combined TMS-EEG to

map cortical excitability and

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connectivity in the brain in real time.

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And finally, pharmacological

interaction studies to dissect

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neurotransmitter specific effects.

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Each of these techniques

has its own strengths.

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For example, EEG, for timing, fMRI

for spatial detail and TMS for

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direct probing of excitability.

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So what happens under

the electrodes in tDCS?

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Let's talk about regional effects.

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When you apply tDCS, you're modulating

membrane polarization of the neurons

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directly under the electrodes.

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For example, the anodal tDCS usually

increases neuronal excitability, and

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the cathode tDCS often reduces it.

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Although this varies by

brain region, and context.

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These effects have been most studied

in the primary motor cortex, where

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changes in motor evoked potentials

provide a relatively straightforward

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measure of cortical plasticity.

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But it's not just about

what happens locally.

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Let's look at remote and

network level effects.

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The brain is a network, not just

a collection of isolated parts.

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So tDCS affects not just the region under

the electrodes, but also functionally

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connected areas through changes in

signal propagation and resting state

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connectivity, including between frontal

cortex and subcortical hubs like

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the ventral tegmental area or VTA.

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tDCS can also strengthen or weaken

communication within large scale

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brain networks, and that has powerful

implications for conditions like stroke

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recovery, chronic psychotic conditions

like schizophrenia and neurocognitive

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disorders like Alzheimer's disease.

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So what's the role of state dependency?

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tDCS is not acting like a

magic button that can turn

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parts of the brain on or off.

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Instead, it appears to be interacting

with what the brain is already doing.

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So if you stimulate using tDCS during

a task, for example, motor training,

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training a particular kind of movement,

memory encoding, so learning a

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new task or learning a new fact or

emotional regulation, the effects can

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be enhanced or changed by the tDCS.

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This kind of an effect is called

state dependent neuromodulation.

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Here are some examples.

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When tDCS is paired with something

like cognitive behavioral therapy,

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it may increase the treatment effects

in people suffering from depression.

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Or when tDCS during rehabilitation

exercises in physical therapy settings,

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when a person is recovering from

a stroke, may potentially improve

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that person's outcomes during their

post-stroke rehabilitation course.

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This insight appears to be shaping

task-concurrent stimulation paradigms

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that integrates tDCS with other

kinds of activities such as behavior

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or other learning paradigms.

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So how about modeling and the

quest for personalized treatment?

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Computational modeling appears

to play a very important

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role in modern tDCS research.

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This helps to predict current flow

through different head anatomies.

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It is guiding electrode placement and

dosage parameters for individual patients.

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It's informing our understanding of

multi-region stimulation effects.

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These kinds of models are among the

most advanced in neurostimulation, and

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they're now helping us to link stimulation

to behavior in more precise ways.

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Overall, this is a step towards

personalized and what are called

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closed loop tDCS protocols.

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So let's talk now about this

connecting brain changes to

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behavior and therapeutic outcomes.

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Ultimately, what matters

most is functional outcomes.

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So can tDCS induced brain changes,

improve memory, reduce depression, or

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enhance recovery after brain injury?

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There's increasing evidence that

it can, but the relationship

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between the neurophysiology and the

behavioral outcomes are complex.

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For example, functional connectivity

changes often correlate with improvements,

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but EEG or MEP changes alone don't

always predict outcomes reliably.

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This particular issue is a major area for

future research, identifying biomarkers

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that bridge the gap between physiological

modulation and real world improvement.

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What are some of the challenges

and clinical implications?

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Research is making progress at lightning

speed, but many questions remain.

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For example, why do some people

respond to tDCS whereas others don't?

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How do genetics, medications, or even

things like the time of day seem to

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affect outcomes from time to time?

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What protocols work best for which

symptoms in which individuals?

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Clinically, this means that we

need better predictive models,

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more tailored protocols and ongoing

research into mechanisms of action.

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Yet the promise remains strong, especially

for conditions marked by network

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dysfunction or impaired neuroplasticity.

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So in closing, tDCS isn't just a

tool for altering mood or memory.

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It appears to be a window

into the brain's plasticity.

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Through these kinds of neurophysiological

measures, it appears as though we're

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increasingly able to track change

optimized treatment protocols and move

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towards individualized personalized care.

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In this chapter, we've explored how

tDCS is both a scientific instrument.

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And a clinical intervention, and the

more we learn about how it shapes

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neural function, the better that we're

going to be able to harness its power

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to improve patient lives and wellness.

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Thanks again for tuning in.

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on the Neurostimulation podcast.