1 Transcranial Direct Current Stimulation Chris Rorden Method Designs Safety.

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Transcranial Direct Current Stimulation

Chris Rordenwww.mricro.comwww.cabiatl.com

MethodDesignsSafety

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tDCS vs TMS

Transcranial magnetic stimulation – Relatively expensive (~$50,000).– Moderate sized effects (e.g. mild speech arrest).– Safe, but there are reports of inducing seizures

when high amplitude and frequency are combined.– Causes resting neurons to fire.

Very brief pulse stops interrupts processing for ~30ms, can be used repetitively.

Depending on frequency, sustained TMS can induce excitability reduction (long-term depression) or enhancements (long-term potentiation) that can persist for hours or days.

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tDCS vs TMS

Transcranial direct current stimulation – Very inexpensive (~$250 for iontophoresis unit).– Believed to be exceptionally safe.– Does not cause resting neurons to fire (Purpura and

McMurtry, 1965; Terzuolo and Bullock,1956).– Believed to modulate the firing rate of active

neurons.Depending on polarity, tDCS can induce cortical

excitability reduction or enhancement can persists for hours.

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tDCS vs TENS

Transcutaneous Electrical Nerve Stimulation systems are used to treat pain.

TENS pulsed 2-160Hz, 5-80 mA.At slow frequency and

high amplitude TENS induces muscle contraction.

In contrast, tDCS uses constant 1-2mA.

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History of tDCS

’50-60s exposed cortex of animals: diminish (cathodal) or enhance (anodal) cortical excitability and activity.

Lippold & Redfearn (1964) report scalp tDCS relieves depression in humans.

Bindman et al. (1964)

+Anodal

-Cathodal

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Why a revival?

New methods provide converging support– Confirmed using consistent behavioral

measures : corticospinal excitability, measured with TMS; TENS (Nitsche 2000; Ardolino 2005).

– Confirmed using imaging: e.g. one sees less task related activation following cathodal stimulation (Baudewig et al., 2001)

– Mechanism: change in membrane potential, NMDA receptor efficacy for longer duration effects (Nitsche, 2004).

Baseline After -tDCS

Baudewig et al. (2003)

Ardolino (2005)Baseline

0min

60min

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Effects persist

Effects of tDCS persist after stimulation ends.Longer stimulation, slower return to baseline.

Nitsche et al. (2003)

9min

7min

5min

Duration

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Typical design

Convention is to conduct behavioral task during and/or immediately after stimulation.

E.G. Dockery reports that prefrontal tDCS polarity influences learning of Tower of London task – with effects seen 6-12 months later.

Dockery et al. (2009)

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Scientific concerns

Current is very small (1-2mA)– So tiny, many doubt neural effects are real.

Behavioral effects typically very small– ‘File drawer problem’ most null results not counted.– Electrode placement crucial.– Controlling for experimenter demand crucial.

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Where to stimulate

Null result if stimulated region not involved with task.

Our Visor neuronavigation system allows you to identify regions based on fMRI or MRI data.

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Where to stimulate

Sadleir et al. (2010) suggest effects will be diffuse.

Datta (2009) suggest high density electrode placement could provide more specificity.

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Where to stimulate

Stimulation region not well focused.

Must create electrical circuit: both anode and cathode.– If both on scalp, are effects due to

facilitation or inhibition?– If one electrode on shoulder/limbs

(Baker, 2010), perhaps spinal influence.

– One option is large, diffuse electrode over mastoid (Elmer, 2009).

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+_

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Clever Hans (1907)

Can a horse perform arithmetic? Actually, animal was responding to body language of

human observers. tDCS effects are small. Small effects vulnerable

to experimenter demand. Double-blind rare but

crucial. I personally remain sceptical

of many findings: we need scientific rigor.

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Our tDCS units

Our tDCS units designed for iontophoresis.

Can deliver up to 4mA: contemporary studies do not exceed 2mA.

Disposable sponge electrodes.

Optional USB system can ensure double blind research.

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Theoretical safety concerns

Potential side effects with tDCS electrode-tissue interface could lead to skin irritation

and damage. Stimulations could lead to excitotoxic firing rates. Tissue damage due to heating.

Rat studies suggest injury only when current density is several orders of magnitude beyond those used in humans (Liebetanz et al. 2009).

Standard doses in humans does not appear to alter serum neuron specific enolase (NSE), a sensitive marker of neuronal damage (Nitsche et al, 2003).

Datta (2009) heating in humans is negligible.

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Practical safety concerns

Subtle but common side effectsNitsche et at. (2003) reports that in more than 500

participants the only side effects are initial scalp tingling or sensation of a light flash.

Some studies suggest that higher current densities can lead to skin irritation.

If cognitive effects are prolonged, perhaps we should warn participants about driving or other hazardous tasks after a treatment session.

• Koenigs (2009) note one neurologically healthy participant reported a couple hours dysphoria following cathodal tDCS.