Y P O C Behavioral Intervention Research T using tDCS O N - PowerPoint PPT Presentation

Y P O C Behavioral Intervention Research T using tDCS O N What to think about? O What guesses do we make? D What do we know and what don’t we?

Disclosure Y P • Scientific Advisory Board Member for O Neuronix, Nexstim, Neosync, Starlab, C Neuroelectrics, Neurostim, Magstim, Axilium T • Serve on Device Expert Panel at FDA O • Funding from National Institutes of Health, N National Science Foundation, Michael J Fox O Foundation, Sidney-Baer Foundation, various D other private Foundations • I will talk about off-label applications of tCS

Dylan Edwards Y P O C T O N O D

Dylan Edwards Y P O C T O N O D

Dylan Edwards Y P O C T O N O D

tCS in Behavioral Research Y P • Why do tCS? O • When do tCS? C • For how long to do tCS? T • How to do tCS? O – How much? N – With what electrode arrangements? O – What electrode size? D

Anodal or Cathodal tCS ? Y P Extra- Cephalic O Cephalic Reference C Reference + + T O N - O - D

Anodal or Cathodal tCS ? Y P O Multiple C “Exit” Electrodes T O N O D Nearly Monopolar Stimulation

Anodal or Cathodal tCS ? Y P O C T O We have a nomenclature problem !! N Do not be fooled by it !! O D

What is tES dose? Y Transcranial Electrical Stimulaiton (tES ) dose is defined by all Y P parameters of the stimulation device that affect the current flow generated in the brain : O X C 1. Electrode Montage : number, shape, size, position. 2. Waveform : Current waveform parameters: pulse width, T amplitude, polarity, repetition frequency; and interval between O stimulation sessions and total number of sessions. N tDCS: Direct Current O Nomenclature defined : Guleyupoglu, Bikson et al. Classification of D Y methods in transcranial electrical stimulation (tES). J Neurosci Methods 2013; 219(2) 287-311 Dose defined : Peterchev, Bikson et al. Fundamentals of transcranial X electric and magnetic stimulation dose: Definition, selection, and reporting practices. Brain Stimulation 2012; (5) 435-53

tDCS dose: Waveform Intensity (mA), Duration (minutes) Ramp (e.g. LTE), repetition… Y P O 2 mA Current intensity Anode (1 mA, 20 min) 30 min) C Cathode (-1 mA, 20 min) 30 min) T -2 mA O N Time Outcome (behavior) + O Linear dose-reponse D - + Intensity -

tDCS dose: Waveform Intensity (mA), Duration (minutes) Ramp (e.g. LTE), repetition… Y P O 2 mA Current intensity Anode (1 mA, 20 min) 30 min) C Cathode (-1 mA, 20 min) 30 min) T -2 mA O N Time Outcome (behavior) + O Non-linear dose-reponse D (none-monotonic) - + Intensity -

tDCS dose: Electrode montage Materials, High-Definition… Number, position, and shape. Y P O C T O N Extra-cephalic 5x5 cm, M1 (anode), “Lateralized” Montage Montage O SO (cathode) D ….

tDCS dose: Electrode montage Materials, High-Definition… Number, position, and shape. Y P (!) Electrode design and preperation is the most important factor for consistent set-up, tolerability, and safety O C • Pad fluid leak (e.g. pressure, view T obstructed) O • Dry out (e.g. pad material, view N obstructed) O • Pad re-use (contamination) D • Critical with High-Definition electrodes (but cannot be ignored with pads)

tDCS dose Y ? P O - C + + + - T O N Simple Goal: To increase excitability in cortex under the anode and decrease excitability under the cathode O (ignore rest of brain) D (!) There is a biophysical basis for polarity specific exctiability changes. But, this simple dose approach is NOT supported by engineering design (or much clinical testing)

Getting from tDCS dose to brain current flow Y P Computational models predict the current Pharmacologic activity Clinical dose is set by O (efficacy and safety) is systemic application flow generated in the brain for a specific C determined by drug (tablets…) stimulation configuration/settings concentration at tissue T O N Electrical activity (efficacy tDCS dose is set by surface and safety) is determined by application (stimulators and O current flow at tissue pads/coils) D

Computational models predict brain current flow Y • Two pad electrodes placed on head and connected to DC P current stimulator. O • Current passed between ANODE(+) and CATHODE(-) • DC CURRENT FLOW across cortex. C • Current is INWARD under ANODE and OUTWARD under CATHODE T Brain current Brain current O intensity direction N O D MRI derived computational model

Individual variability of tDCS: anatomy Truong et. al. Neuroimage Clinical 2013 D Y P O C T O N • Evaluated range of conventional and HD tDCS montages O • Male/female, super-obese/low-BMI… D • Considered magnitude of peak current in brain • Location of peak current inside brain • Maximum stimulator voltage (safety) • Current density at scalp (sensation)

tDCS in children Kessler Dosage considerations for transcranial direct current stimulation in E Y children: a computational modeling study. PLoS One 2013 P O C T O N O D

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What do we know? Y P • Does not lead to neuronal firing O – Purely modulatory C – Combination with other interventions • Does change firing rate likelihood of neuronal ensembles T – Polarity dependent O – Neuronal network impact N – Shifts oscillatory brain activity O • Bipolar D – Both anode and cathode have an effect – Entry and exit electrodes – Can be ‘almost monopolar’

Neurons? Which ones? Y P O C T O N O D • Pyramidal Neurons? • Glia? • Axon hillocks? • Dendritic branches?

Neurons? Which ones? Y + P O C T O N O D

Theory of neuron polarization by tDCS Y P O C T Current flow outward inward O N O D

Theory of neuron polarization by tDCS Y P O Head Surface C T Current flow outward inward O Cortical Neuron N O D

Theory of neuron polarization by tDCS Y P O Head Surface C T Current flow Current Hyperpolarized cell Flow outward inward O compartments N O Depolarized cell D compartments ? Increased Excitability / Plasticity

Theory of neuron polarization by tDCS Y P O Head Surface C T Current flow Current Depolarized cell Flow outward inward O compartments N O Hyper-polarized cell D compartments Decreased Excitability / Plasticity

Modulation of “excitability” under DCS Y Depolarized soma P Increased O Excitability / C Plasticity T Current flow outward inward O Hyperpolarized soma N Decreased O Excitability / Plasticity D

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tDCS modifies MEP’s Y P O C T O N O D

Can tDCS modify other ‘behaviors’ ? Y P O C Did it T feel the O same? N O D What brain region helps respond to that question? Beware of circular ‘experimental designs’

Brain Behavior Relations Y Genetic Defect Environmental Factors Acquired Insult P O C Pathology T Brain Adaptation/ Compensation Change in Cognitive Strategy O N O Pattern of Brain Activity D Behavior Symptoms of Disease

Neurons or Networks ? Y P O 10 12 Neurons C 10 4 Connections T per neuron O 10 18 Synapses N O D

Modulating Brain’s Intrinsic Activity with tDCS Y P O C T O N O D

Modulating Brain’s Intrinsic Activity with tDCS Y P O C T O N O D

Modulating Brain’s Intrinsic Activity with tDCS Y P O C T O N O D

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Targeting brain patterns (& Y oscillations) with tDCS / tACS P O C T O N O D Rs-fcMRI with Subgenual Simulated E field Collaboration with Giulio Ruffini and StarStim

What do we know? Y P • Safe if done correctly O • Easy to apply DEPENDS ON DOSE !! C • Double blinding possible Davis et al Eur J Neurosci. 2013 T – Subject cannot tell whether anodal or cathodal O – Subject cannot tell whether sustained or transient stim N O Real D Sham

Why do tDCS ? Y P • Modify brain activity during stimulation O and beyond C • Affect behavior T O • Causal relations between brain activity and N behavior • Prime brain activity to ‘enhance’ impact of O behavioral intervention, task performance D

When do tDCS ? Y P • Before – During – After Task O C Task T O Before N Offline O During - Online D After - Offline

For how long to do tDCS ? Y P O C Task T How long does the effect last? O N O D • Membrane effect • Network impact with induction of plastic changes • ? LTP- or LTD-like effects

For how long to do tDCS ? Y P Task Related Changes O in Brain Activity Anticipatory Reflective Brain C Task Preparatory Activity Brain Activity - Consolidation T O N O • Interaction between tDCS and ongoing brain activity in the brain D • Nature of the task may affect the nature of the effects of tDCS • Different tasks may modify tDCS effects differently • More/longer tDCS may not necessarily mean more of the same effect • Physiologic measures in addition to behavioral measures desirable