Duke.Sept21,2016
MaromBikson,Ph.D.
TheCityCollegeofNewYork
Engineeringprinciplesoftranscranial
DirectCurrentS4mula4on
LucasParra,AsifRahman,NiranjanKhadka,Jacek
Dmochowski,DorisLing,MarkJackson,Dennis
Truong,BelenLafon,GregoryKronberg,OleSeibt,
DevinAdair,NigelGebodh
Disclosure:
SoterixMedicalInc.producestDCSandHigh-Defini4on
tDCS.MaromBiksonisfounderandhassharesinSoterix
Medical.Someoftheclinicaldatapresentedmaybe
supportedbySoterixMedicalMaromBiksonserveson
thescien4ficadvisoryboardofBostonScien4ficInc.
Support:
NIH(NINDS,NCI,NIBIB),NSF,EpilepsyFounda4on,
WallaceCoulterFounda4on,DoD(USAF,AFOSR)
Sides at NeuralEngr.com
What is Neuromodulation?
•  Application of electricity to
change brain function
•  Often therapeutic
•  Many techniques: Name of each
method is defined by how
electricity is delivered
(some letters ending with “s”).
C
Deep Brain
Stimulation (DBS)
B
Transcranial
Magnetic Stimulation
(TMS)
A
Transcranial Direct
Current Stimulation
(tDCS)
Why Neuromodulation?
•  To probe the brain for science
•  To treat the brain: neurological,
psychiatric, rehabilitation
•  To enhance mental performance
( neuro-enhancement )
C
Deep Brain
Stimulation (DBS)
B
Transcranial
Magnetic Stimulation
(TMS)
A
Transcranial Direct
Current Stimulation
(tDCS)
What
Whatis
istDCS?
tDCS?
transcranial
transcranialDirect
DirectCurrent
CurrentStimulation
Stimulation
tDCScurrentflow
•  Two pad electrodes placed on head and connected to DC
current stimulator.
•  Current passed between ANODE(+) and CATHODE(-)
•  DC CURRENT FLOW across cortex.
•  Current is INWARD under ANODE and OUTWARD under
CATHODE
Brain current
intensity
Brain current
direction
MRI derived computational model
tDCScurrentflow:anodeandcathode
Electro
de
HeadSurface
Currentflow
outward
inward
Cor4calNeuron
tDCScurrentflow:anodeandcathode
Anode
(+)
HeadSurface
Currentflow
outward
inward
Hyperpolarizedcell
compartments
Current
Flow
Depolarizedcell
compartments
?IncreasedExcitability/Plas4city
tDCScurrentflow:anodeandcathode
Cathod
e (-)
HeadSurface
Currentflow
outward
inward
Depolarizedcell
compartments
Current
Flow
Hyper-polarizedcell
compartments
Decreased Excitability / Plasticity
What is tDCS?
transcranial Direct Current Stimulation
+
Weak direct
current applied
across the head
=
To change brain
function in healthy
and sick individuals
To make us
smarter and
better
Accelerated Training
HRL
Electro-doping
Electroceuticals: Brain healing
What is all the hype about?
“Electro-doping”
Transcranial Direct Current Stimulation (tDCS)
-
•  Non-invasive, portable (9V), welltolerated neuromodulation.
•  Low-intensity (mA) current passed
between scalp electrodes.
•  Tested for cognitive neuroscience
and neuropsychiatric treatment.
Depression,Pain,Migraine,Epilepsy,PTSD,
Schizophrenia,Tinnitus,Neglect,Rehabilita4on(motor,
tDCS Publications
aphasia),TBI,OCD,A]en4on/Vigilance,Accelerated
learning(reading,motorskills,math,threatdetec4on),
Memory,Crea4vity,Sleep(SW,Luciddreaming,Threat
detec4on,Impulsivity,Compassion,Jelousy,Reality
Filtering,IQ,Prejudice…
Ø How can a 9V battery do anything for
the complex brain?
Ø How is specificity of action achieved ?
How could Pharmaceuticals
treat so many disorders?
It’s not one thing.
Many formulations.
How could tDCS treat
many disorders?
It’s not one thing.
Many “formulations”.
tDCS electrode position on the head
determines which regions are stimulated
Max
Zero
ü  Specific brain regions are associated with
specific functions / disease
Truong et al. Clinician accessible tools for GUI computational
models. “BONSAI” and “SPHERES”. Brain Stimulation 2014
High-Definition tDCS uses arrays of
electrodes to focus current to targets
ü  Software allows you to generate subject
and target specific (HD) tDCS “formulation”
Dmochowksi et al. Optimized multi-electrodes stimulation increases
focality and intensity at target. J Neural Engr 2011
“4x1” montage of High-Definition tDCS
Max
Zero
ü  Allows targeting of selected cortical regions
Datta et al. Gyri-precise model of tDCS: Improved spatial focality
using a ring versus conventional pad. Brain Stimulation 2009
“4x1” montage of High-Definition tDCS
•  Centerelectrodedetreminespolarity
Ø  Uni-direc=oalmodula=on
•  Ringradiusdeteminescor=calfocality
Ø  Skullresisi=vyisnottheproblem
Cathode
Center
Anode
Center
Outward
Inward
Alam et al. Spatial and polarity precision of concentric HD-tDCS.
Phys. Med. Biol. 2016
tDCS montages for treatment of Depression
•
•
•
•
•
Brunoni et al.
SELECT / ELECT
target: DPLPC
2.0 mA
Double blind RCT
•
•
•
•
•
Loo et al.
Multi-Center Trial
target: DPLPC
2.5 mA
Double blind RCT
•  Target stimulated but not specifically
Seibt al. The pursuit of DLPFC. Brain Stimulation 2015
How could weights helps
with so many sports?
It’s a tool to enhance
specific training.
How could tDCS treat
many disorders?
It’s tool to enhance cognitive
training and therapy.
tDCS combined
with training
(tasks)
How does tDCS just enhance
the trained task?
+
Cellular mechanism:
Functional Targeting
(selectivity)
Bikson et al. Origins of specificity during tDCS: anatomical, activityselectivity, and input-bias mechanisms. Front Human Neuro 2013
BiophysicalbasisoftDCStaskselec4vity
① tDCSproducesa
sustainedweak
polariza4onof
neuronalmembranes
② Weakpolariza4on
modulatescor4cal
processingrelatedto
ac#vetasks,andcan
promoteplas4city
(learning)
tDCS:Sustainedweakpolariza4on
Brain slice: Optical Mapping with Voltage Sensitive Dyes
DCOn
DirectCurrent
(~ 0.2 mV)
Bikson et al. Effects of uniform extracellular DC electric fields on
excitability in rat hippocampal slices. J Physiol 2004
tDCS:Sustainedweakpolariza4on
Intracellularrecordingandmorphology
0mV
polariza=on
1V/mDirect
Current
0.3mV
polariza=on
DirectCurrent
0.1mV
polariza=on
Radman, Bikson et al. Role of cortical morphology in uniform
electric field stimulation. Brain Stimulation 2009
tDCS:SustainedAXONTERMINALweakpolariza4on
FromAnatomicalTarge4ngtoTaskTarge4ng
Networkofinterest(e.g.
depression,mathcells)
Othernetworks–nottargets
forneuromodula4on
Preferen4almodula4onof
selectedac4veneurons
Currentflowacross
en4reregion
Bikson et al. Origins of specificity during tDCS. Front Human Neuro 2013
BiophysicalbasisoftDCStaskselec4vity
Fritsch 2010: BDNF dependent +
activity dependent induction
Specificongoing
synap=cac=vity
(noplas=city)
DC + Theta burst synaptic
activity
tDCSinduces
plas=city
Rahman 2015: Pathways specific
+ plasticity dependent modulation
Ongoing
Plas=city
“Noneac=ve”
synapse
tDCSmodulates
plas=city
NotDCS
synap=c
plas=city
Synaptic Plasticity in
brain slice
Weakpolariza4onmodulatessynap4cefficacy
Excitatory post-synaptic currents
(field) in brain slice
Train of synaptic ongoing activity
Direct Current
•  Ongoing synaptic activity modulated while
tDCS sustained
•  Substrate for plasticity
•  Modulation of ongoing activity, not generation
BiophysicalbasisoftDCStaskselec4vity
① tDCSproducesa
sustainedweak
polariza4onof
neuronalmembranes
② Weakpolariza4on
modulatescor4cal
processingrelatedto
ac#vetasks,andcan
promoteplas4city
(learning)
Weakpolariza4onmodulatessynap4cefficacy
•  Polarity of modulation
depends on many
factors
Rahman et al. Cellular effects of DC Stimulation: Somatic and
Terminal effects. J Physiol 2013
Direct Current Stimulation of Network Oscillations
NetworkGammaAc4vity
BrainSlice
NetworkModel
Anode DCS (6 V/m)
Excitatoryneuron/inhibitoryneuronnetwork
adapta4on
adapta4on
Reato et al J Neurosci 2010
Cathode DCS (-6V/m)
tDCS is tested for so
(too?) many things.
Ø How can a 9V battery do anything for the brain?
Ø How is specificity of action achieved ?
tDCS generates weak current across specific
parts of the brain. Neurons in those parts are
polarized for the duration.
+ Tasks applied at same time leading to
specific brain activity and plasticity.
= tDCS changes how those specific parts process
this activity, which boosts training and learning.
Computa4onalmodelsofbehavior
Reato et al. Transcranial electrical stimulation accelerates human
sleep homeostasis. PLOS Computation Biology 2013
Duke.Sept21,2016
MaromBikson,Ph.D.
TheCityCollegeofNewYork
Engineeringprinciplesoftranscranial
DirectCurrentS4mula4on
LucasParra,AsifRahman,NiranjanKhadka,Jacek
Dmochowski,DorisLing,MarkJackson,Dennis
Truong,BelenLafon,GregoryKronberg,OleSeibt,
DevinAdair,NigelGebodh