Slides From NIMH-sponsored tES Workshop Held September 29th and 30th at NIH

An email from Michelle Pearson at the NIH (because I had signed up for the online version of the workshop) alerted me today to a trove of TES (Transcranial Electric Stimulation) info being made available to us. Presenter slides (in PDF form) from the workshop were available for download. Because the download process was pretty wonky, involving many clicks and declined logins to Dropbox I thought to make them available here as well.

1-lisanby-introductory-remarks Sarah Hollingsworth Lisanby, M.D., NIH
2-rumsey-introduction Judy Rumsey, Ph.D.
3-wassermann-historical-overview Eric Wassermann, M.D., NINDS
4-parra-tdcs-mechanisms Lucas Parra, co-founder of Soterix Medial Inc. @lcparra1
5-frohlich-tacs-mechanisms @FlavioFrohlich, University of North Carolina-Chapel Hill
6-clark-combining-imaging-and-stimulation Vincent P. Clark, PhD Mind Research Network
7-woods-tes-technical-aspects Adam J. Woods, PhD @adamjwoods
8-richardson-blinding Jessica D. Richardson, Ph.D.
9-kappenman-reproducibility Emily S. Kappenman
10-bikson-computational-modeling-design Marom Bikson, CCNY @MaromBikson
11-deng-anatomical-variability-efields Zhi-De Deng, Ph.D., NIH
12-dmochowski-targeted-stimulation-sources Jacek P. Dmochowski, CCNY
13-loo-depression-trials Colleen Loo, Black Dog Institute
14-brunoni-neuropsychiatry-large-trials André R. Brunoni, @abrunoni
15-cohen-motor-learning Leonardo G. Cohen, M.D. NINDS
16-edwards-augmentation-neurorehabilitation Dylan J. Edwards PhD
17-lim-ongoing-trials Kelvin O. Lim, M.D.
18-frohlich-tacs-psychiatry-trials @FrohlichLab
19-charvet_remote-tdcs Leigh Charvet PhD, NYU

Early Torpedo Fish TES Researcher. From the Wassermann Historical Overview slides

Early Torpedo Fish TES Researcher. From the Wassermann Historical Overview slides

Adam Gazzaley | ShrinkrapRadio.com

Adam Gazzaley TedX Sonoma 2015

Adam Gazzaley TedX Sonoma 2015

We’ve covered Dr. Adam Gazzaley director of the Gazzaley Lab at UCSF previously so I was excited to see he was being interviewed for one of my favorite podcasts, ShrinkrapRadio by Dr. David Van Nuys. I’m a big fan of Dr. Dave and have been enjoying his interviews with top psychologists for years. (Especially those with Jungian analysts.) I’ve clipped an excerpt of the interview that deals directly with tDCS and brain stimulation below but I highly recommend checking out the entire episode as it provides an excellent framework for understanding the notion of brain training using technology including video games designed specifically to enhance memory and cognition.

In this clip Dr. Gazzaley lays out what clearly is the near-future of non-invasive brain stimulation… You’re playing a video game that has been optimized to enhance working memory (for example). At the same time your EEG is being monitored for brain activity. According to the EEG data, tDCS (tACS, tRNS etc) is activated for the purpose of enhancing activity in that region of your brain. As your game accuracy increases, the game adapts to increase difficulty to an optimum training level. Loop!

Here’s a 2 minute clip from Dr. Dave’s interview with Adam Gazzaley

Dr. Gazzaley’s (@adamgazz co-founder with @EddieMartucci) company, Akili (@AkiliLabs), just announced (1/22/16)  $30.5 million in funding. Interesting, Akili is part of the PureTech (@PureTechH) family of companies we covered recently (Tal Medical).

A few of Dr. Gazzaley’s papers you might find interesting.
Video game training enhances cognitive control in older adults Nature (pdf)
Effects of noninvasive brain stimulation on cognitive function in healthy aging and Alzheimer’s disease: a systematic review and meta-analysis. (pdf)

Dr Gazzaley’s  (Nov 2015) Ted Talk

Anodal tDCS over the Primary Motor Cortex Facilitates Long-Term Memory Formation Reflecting Use-Dependent Plasticity

Sham or anodal tDCS (1 mA) was applied for 20 min during motor practice and retention was tested 30 min, 24 hours and one week later. All subjects improved performance during each of the two sessions and learning gains were similar. Our main result is that long term retention performance (i.e. 1 week after practice) was significantly better when practice was performed with anodal tDCS than with sham tDCS. This effect was large  and all but one subject followed the group trend. Our data strongly suggest that anodal tDCS facilitates long-term memory formation reflecting use-dependent plasticity. Our results support the notion that anodal tDCS facilitates synaptic plasticity mediated by an LTP-like (long-term potentiation) mechanism, which is in accordance with previous research.

Longitudinal Neurostimulation in Older Adults Improves Working Memory | PLOS ONE

tdcsLongitudinalOlderAdults.jpg

Modeling of current flow when applying 1.5 mA tDCS for F4 anodal (top) and P4 anodal (bottom) stimulation and the cathodal electrode placed on the contralateral cheek.

Important study. 72 older participants, average age 64 showed improvement in working memory tasks but also (and this is a big deal where it comes to cognitive enhancement) significant transfer (where improvements are seen in other tasks not specifically trained for). These results run counter to other recent studies and beg the question of whether the participant’s age was a factor. i.e. Is tDCS more effective for aging brains? That would be a big deal. [See Also: tDCS selectively improves working memory in older adults with more education]  And thanks to PLOS ONE we can all read the full paper (linked below)

The results demonstrated that all groups benefited from WM training, as expected. However, at follow-up 1-month after training ended, only the participants in the active tDCS groups maintained significant improvement. Importantly, this pattern was observed for both trained and transfer tasks. These results demonstrate that tDCS-linked WM training can provide long-term benefits in maintaining cognitive training benefits and extending them to untrained tasks.

Interesting, the location of the reference (cathodal) electrode was opposite cheek.

In all conditions, one electrode was placed over the target location at either F4 or P4 (International 10–20 EEG system) and the reference electrode was placed on the contralateral cheek.

via PLOS ONE: Longitudinal Neurostimulation in Older Adults Improves Working Memory.

Wearable functional Near Infrared Spectroscopy (fNIRS) and tDCS: Expanding Vistas for Neurocognitive Augmentation | Frontiers

A new generation of functional near infrared spectroscopy (fNIRS) systems is described that are miniaturized, portable, and include wearable sensors. These developments provide an opportunity to couple fNIRS with tDCS, consistent with a neuroergonomics approach for joint neuroimaging and neurostimulation investigations of cognition in complex tasks and in naturalistic conditions. The effects of tDCS on complex task performance and the use of fNIRS for monitoring cognitive workload during task performance are described. Also explained is how fNIRS + tDCS can be used simultaneously for assessing spatial working memory.

via Frontiers | Wearable functional Near Infrared Spectroscopy (fNIRS) and transcranial Direct Current Stimulation (tDCS): Expanding Vistas for Neurocognitive Augmentation | Frontiers in Systems Neuroscience.

Frontiers | Open questions on the mechanisms of neuromodulation with applied and endogenous electric fields

via @MaromBikson Download links below.

Despite increased knowledge, and more sophisticated experimental and modeling approaches, fundamental questions remain about how electricity can interact with ongoing brain function in information processing or as a medical intervention. Specifically, what biophysical and network mechanisms allow for weak electric fields to strongly influence neuronal activity and function? How can strong and weak fields induce meaningful changes in CNS function? How do abnormal endogenous electric fields contribute to pathophysiology? Topics included in the review range from the role of field effects in cortical oscillations, transcranial electrical stimulation, deep brain stimulation, modeling of field effects, and the role of field effects in neurological diseases such as epilepsy, hemifacial spasm, trigeminal neuralgia, and multiple sclerosis.

via Frontiers | Open questions on the mechanisms of neuromodulation with applied and endogenous electric fields.

The anodal tDCS over the left posterior parietal cortex enhances attention toward a focus word in a sentence | Frontiers in Human Neuroscience

In order to activate the left PPC (atDCS), the anodal electrode was placed over P3 in accordance with the 10–20 international system. The cathodal electrode was attached to the contralateral supraorbital area.

Fig2a

Head locations for the electrodes. The target region was the left posterior parietal cortex where the center of the electrodes was located at P3 in the 10–20 international measurement. The reference patch was located just above the eyebrow.

 

via Frontiers | The anodal tDCS over the left posterior parietal cortex enhances attention toward a focus word in a sentence | Frontiers in Human Neuroscience.

YOUR ELECTRIC PHARMACY

Emphasis mine on “but over time it will also gradually rewire your neurons to prevent future attacks.” Very interesting considering the source, Marom Bickson. If you’ve been following the pop press on brain plasticity, you’ve certainly heard the phrase: “Neurons that fire together, wire together.” Could this be a meta-framework for thinking about tDCS?

Head band and controller sourced from CaputronMedical.com

Head band and controller sourced from CaputronMedical.com the green electrode/strap on the right is the Soterix EasyStrap (see below)

Future medications for brain disorders could be delivered through electrodes rather than pills
By Marom Bikson and Peter Toshev

The pharmacist guides you to a shelf of headgear, labeled
with different brain regions. She fits you for a cap, the underside of which features thin conductive metal strips, called electrodes, coated in adhesive gel to stick gently to your scalp.
The electrodes link to a slim cable that dangles from the back of the cap. She then hands over the key component of your prescribed medication: an electric stimulator.
Once a day for the next week you will don the headgear
and plug the cable into this device for a 20-minute dose of
electricity. Setting aside your trepidation, you give it a try in front of the pharmacist. At first you feel only a tingling sensation and then relief.
As you wear the cap, an electric current is traveling from
the electrodes, past hair, scalp and bone, into the brain regions responsible for your migraines. At first it merely blunts the pain, but over time it will also gradually rewire your neurons to prevent future attacks. The pharmacist explains that you will be free to carry on with your day—finish chores, watch television, go for a walk– with the cap on your head, and when the dose is up, the stimulator will simply stop running.
——–
When brain cells activate together, the connections among them grow stronger and more numerous. Cells that seldom fire in concert gradually lose their linkages. Adding tDCS can therefore heighten the brain’s ability to rewire itself—its plasticity.

Source: http://neuralengr.com/wp-content/uploads/2014/10/samind_2014_11.pdf
See also: Zap Your Brain to Health with an Electrode Cap – Scientific American.
And: Giving the Brain a Buzz: The Ultimate in Self-Help or a Dangerous Distraction?

Soterix Accessories page. (I am not affiliated with Soterix or any other product mentioned on this blog).

Polarity Specific Suppression Effects of Transcranial Direct Current Stimulation for Tinnitus

Tinnitus is the perception of a sound in the absence of an external auditory stimulus and affects 10–15% of the Western population. Previous studies have demonstrated the therapeutic effect of anodal transcranial direct current stimulation tDCS over the left auditory cortex on tinnitus loudness, but the effect of this presumed excitatory stimulation contradicts with the underlying pathophysiological model of tinnitus. Therefore, we included 175 patients with chronic tinnitus to study polarity specific effects of a single tDCS session over the auditory cortex 39 anodal, 136 cathodal. To assess the effect of treatment, we used the numeric rating scale for tinnitus loudness and annoyance. Statistical analysis demonstrated a significant main effect for tinnitus loudness and annoyance, but for tinnitus annoyance anodal stimulation has a significantly more pronounced effect than cathodal stimulation. We hypothesize that the suppressive effect of tDCS on tinnitus loudness may be attributed to a disrupting effect of ongoing neural hyperactivity, independent of the inhibitory or excitatory effects and that the reduction of annoyance may be induced by influencing adjacent or functionally connected brain areas involved in the tinnitus related distress network. Further research is required to explain why only anodal stimulation has a suppressive effect on tinnitus annoyance.

via Polarity Specific Suppression Effects of Transcranial Direct Current Stimulation for Tinnitus.
HatTip Reddit user matt2001

Skin Lesions Induced by Transcranial Direct Current Stimulation tDCS

However, in all three instances,the skin lesions occurred under the cathode supraorbital regionat the end of the sessions. By separating the electrodes from the skin they presented small skin lesions, which resembled red burns, with small blisters Fig.1. The extension of the lesions ranged from 2 to 3 mm up to 1.5 cm. Lesions appeared after the second stimulation session in one patient, while for the other two, they appeared between the eighth and tenth sessions. None of the patients had a skin lesion before the start, skin disease or a history of any pathological skin disorder

via Skin Lesions Induced by Transcranial Direct Current Stimulation tDCS – 532.pdf.

Articles of Note – March 2013

(What happened to February?)
Transcranial Direct Current Stimulation (tDCS) of the visual cortex: a proof-of-concept study based on interictal electrophysiological abnormalities in migraine (pdf)
with anodal tDCS turned out to be beneficial in MoA (migraine without aura patients) migraine attack frequency, migraine days, attack duration and acute medication intake significantly decreased during the treatment period compared to pre-treatment baseline
Tags: Migraine, visual cortex,

The Mental Cost of Cognitive Enhancement (pdf)
Stimulation to the the posterior parietal cortex facilitated numerical learning, whereas automaticity for the learned material was impaired. In contrast, stimulation to the dorsolateral prefrontal cortex impaired the learning process, whereas automaticity for the learned material was enhanced.
Wired Version
New Scientist Version
Tags: Roi Cohen Kadosh,

Keith Spalding’s Simple DIY TDCS circuit using CRDs
A DIY schematic for tDCS using CRDs for current regulation.
Tags: DIY, CRD

Noninvasive transcranial direct current stimulation over the left prefrontal cortex facilitates cognitive flexibility in tool use
…we hypothesized that cathodal (inhibitory) transcranial direct current stimulation (tDCS) will facilitate performance in a flexible use generation task.
The results support the hypothesis that certain tasks may benefit from a state of diminished cognitive control.
Tags: inhibitory benefits,

When Anger Leads to Rumination
Induction of Relative Right Frontal Cortical Activity With Transcranial Direct Current Stimulation Increases Anger-Related Rumination
…results suggest that anger associated with greater relative left frontal cortical activity predicts approach-oriented aggressive action, whereas anger associated with greater relative right frontal cortical activity predicts inhibited rumination.

Potential of transcranial direct current stimulation shown in fibromyalgia
Transcranial direct current stimulation delivered focally to the left primary motor cortex of patients with fibromyalgia significantly reduced perceived pain compared with sham stimulation in a proof-of-principle pilot trial.
Tags, fibromyalgia, pain

NIBS Non-Invasive Brain Stimulation – The Air Force Research Laboratory and tDCS

NIBS Non-Invasive Brain Stimulation

Every military application of tDCS I’ve seen so far specifically mentions drones and drone pilot training. This logo has a drone in it! For the record, I think the use of drones is illegal and immoral, and that the deaths of innocents is un-American and unacceptable. That said, the tDCS research coming out of this sector is fascinating and will no doubt have an impact beyond military training.

[Update 7/30/14 I’ve replaced the old (broken) link with an active one that comes via Ryan (see comment below)] http://colonyofcommodus.files.wordpress.com/2013/02/2012-afosr-review-mckinley.pdf it was a public document. It appears to be a set of slides used in a presentation. It documents the most aggressive use of tDCS for the purpose of learning and cognitive enhancement I’ve seen. You will conclude, after reading this, that the Air Force is not fooling around.

Air Force Research Laboratory Skill Learning tDCS

Here is one of the more shocking aspects of the research: The notion that cathodal stimulation can have a positive effect by depressing ‘competing memory’. What? The plot thickens.

Air Force Research Laboratory Skill Learning tDCS

There is weeks of research ahead for anyone diving deeply into this paper. A lot of new questions to answer.

Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory – Springer

[Update 12/17/2012 Another paper discussing the efficacy of using tDCS to enhance working memory. Transcranial direct current stimulation of the prefrontal cortex modulates working memory performance: combined behavioural and electrophysiological evidence]

Working memory, as associated with ‘brain training’ and ‘plasticity‘, is often expressed as what one would wish to have more of, or at the very least, what one hopes not to lose as we age. (For a great overview of working memory and the how’s of enhancing it, see this fascinating post from neuroscientist Bradley Voytek’s blog  Working memory and cognitive enhancement.)

Our aim was to determine whether anodal transcranial direct current stimulation, which enhances brain cortical excitability and activity, would modify performance in a sequential-letter working memory task when administered to the dorsolateral prefrontal cortex DLPFC. Fifteen subjects underwent a three-back working memory task based on letters. This task was performed during sham and anodal stimulation applied over the left DLPFC. Moreover seven of these subjects performed the same task, but with inverse polarity cathodal stimulation of the left DLPFC and anodal stimulation of the primary motor cortex M1. Our results indicate that only anodal stimulation of the left prefrontal cortex, but not cathodal stimulation of left DLPFC or anodal stimulation of M1, increases the accuracy of the task performance when compared to sham stimulation of the same area. This accuracy enhancement during active stimulation cannot be accounted for by slowed responses, as response times were not changed by stimulation. Our results indicate that left prefrontal anodal stimulation leads to an enhancement of working memory performance. Furthermore, this effect depends on the stimulation polarity and is specific to the site of stimulation. This result may be helpful to develop future interventions aiming at clinical benefits.

via Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory – Springer.
full pdf

This 2011 paper does confirm positive results of tDCS in a similar application and test setup. Improving working memory: exploring the effect of transcranial random noise stimulation and transcranial direct current stimulation on the dorsolateral prefrontal cortex.

However, the study does provide confirmation of previous findings that anodal tDCS enhances some aspects of DLPFC functioning.

Transcranial Direct Current Stimulation (TDCS) Targeted Using Brain Imaging Accelerates Learning

From (I believe) a talk in 2010 given at the Organization for Human Brain Mapping by Dr. Vince Clark, director of the Clinical Neuroscience Center at the  University of New Mexico (and previously, director of the Mind Research Network). The slides reference a study where tDCS was used in training subjects to accurately detect hidden and camouflaged objects, as in a military setting. What caught my eye, something I don’t recall seeing anywhere else, is the comparison of effectiveness of different amounts of current. It begs the question: If 2 mA is more effective than 1 mA, what about 3 mA? [As Peter points out in his comment, the chart actually contrasts effects of 2 mA and  0.1 mA as a control. I do still think it’s a good question: Why 2 mA?]. Much I don’t understand in the slides without the talk to go along with, but have a look  pdf, Quick View. And a link (abstract) to what appears to me a follow-up study. P.S. After tracking all this down I can’t tell you how frustrating it is to not be able to access the full texts of these studies, especially when we (NiH, DOD) paid for them. If you can get me a copy I would
greatly appreciate it.

mind Research Network Vince Clark 1

mind Research Network Vince Clark 2

 

Neuroscience: Brain buzz : Nature News

Effects seen after the electricity is shut off can last for an hour or so and seem to arise from a second mechanism. Pharmacological evidence suggests that the current increases the expression of proteins called NMDA receptors at the synapses, the connections between neurons. This heightens the plasticity of brain tissue — leaving it in a temporary state somewhat like wet clay, in which it is more apt to reshape its synaptic connections in response to stimuli, such as when learning a video game.

Researchers are exploring the ways in which this wet-clay state can be exploited. In a 2009 study6, Leonardo Cohen at the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland, showed that tDCS improved people’s ability to learn a simple coordination exercise — and that the improvement was still apparent three months after the experiment ended. Such results have led to an interest in stroke rehabilitation strategies. Small trials by Cohen, Nitsche, and others have shown improved recovery of hand function when tDCS is used this way.

via Neuroscience: Brain buzz : Nature News.
pdf