Using electricity to try and zap away maladies of the brain is a thousand years old but how far we have really come? Known as transcranial direct current stimulation, or tDCS, today, it is still hit or miss.

Zapping Away the Pain

In 400 BC the Greek’s used the torpedo fish (also called an electric ray) to zap pregnant women to numbness when they were giving birth. They did not know what caused this numbness but since then the torpedo fish became popular in medicine among the Greeks, Romans and Persians as a way to try and zap away headaches, muscle pain, vertigo and just about anything else.  The torpedo fish has to be alive to produce electricity.  In full strength it delivers over 30 milliamps of current that could potentially kill you.  A fatigued fish however delivers only enough to numb you. Presumably this ancient medicine involved an intimate understanding of the state of the fish. (Close your eyes and imagine that treatment!).

It was not until Luigi Galvani discovered animal electricity in 1780 that the mysterious force of the torpedo fish became known.  Yet even a few decades before Galvani discovered animal electricity, other folks like Von Kleist had discovered how to generate and control electricity which led to the use of electric shock therapy in medicine as early as 1757.  The person who perhaps pulled this all together was Galvani’s nephew Giovanni Aldini who not only took on the mantle of defending his Uncle’s discovery of bioelectricity, but stated the objective of this research as being to:

“Convey an energetic fluid to the seat of all sensations; distribute its force throughout the different parts of the nervous and muscular systems; produce, reanimate and, so to speak, control the vital forces.”

In this regard he traveled around the country applying direct currents to the heads of mental health patients claiming to cure them of all sorts of maladies.  He did even apply it to himself to test it out, describing the experience as a jolt against the inner surface of his skull that left him an insomniac for several days.

Zapping Away Mental Malady

Giovanni’s best documented success was of Luigi Lanzarini, a farmer who had been confined to an asylum in Bologna suffering from ‘melancholy madness’ (today called depression) but was cured after just a few weeks of treatment.  This was 1801.  This transcranial direct current stimulation (tDCS), also called neurostimulation or neuromodulation, or galvanism as it was referred to by Aldini, found some traction in the mental health community through the 19th century.  In the late 1800s Joseph Wiglesworth, Superintendent of the Rainhill asylum in northern England tried it on his patients.

[see related post Lunatic Asylums of the 1800s]

He found that three improved enough to be discharged, three more improved significantly, 1 improved slightly and 5 showed no change. Wiglesworth was not blown away by the results, writing that ‘it is not going to revolutionize the treatment of insanity’.

Easy Zapping for Consumers

Fast forward some 120 years to the 21^st century and the neuroscience community is still trying to zap away pain, fatigue, sadness and psychosis and anything else that ails you.  Thync, a company that popped up in the last several years sold a tDCS device to consumers with two settings – one that they claimed would zap you into an alert state and the other that would calm you down. The reviews were mixed (for example see here).  Some claimed it worked, others claimed it had no effect and still others reported that it made them feel clammy or made their heart race.  Suffice to say it has now been pulled from the market and in place of it their website now describes them as an R&D company and showcases some scientific papers on the safety and efficacy of their stimulation protocol.

Generally, in academia and clinical use, the stimulation protocols vary from 1-2 milliamperes (mA).  (at 1 mA you can already feel it as a tingling sensation, 5 mA can result in severe pain, 7 and above has a good chance of stopping your heart). Thync’s paper in PeerJ [1] studies a protocol that involves ramping up the current to 2 mA over 30 seconds, sustaining it for 20 minutes and then ramping it back down.  The paper claims that <5% reported adverse physical side effects such as nausea, headaches, dizziness, or difficulty breathing.  This may well be true but what about the therapeutic effects?  A bioRxiv paper [2] lays out results that compare self-reported feelings of drowsiness, alertness, sleep quality and mood before and after using a tDCS treatment of the trigeminal nerve for one week.  The results were pretty small (10-15% self reported improvements) but sufficient to meet the p<0.05 criteria.

Placebo effects are difficult to rule out in this experimental paradigm because even sham controls are not really shams for a treatment that you can actually feel as mild itching or tingling (the shams ramp up the current to 2 mA over 30 s but don’t sustain it, shhh, don’t tell). Other confounds such as greater self-care and awareness when performing a self-experiment are also difficult to rule out. There is also the challenge of substantial inter and intra person variability which is difficult to parse.  (see also related post Human Brains and the Control Issue).  Moreover, the results here are shown as group averages which also conveniently obscure the individual results – did everyone uniformly improve just a little or did some people improve a lot and others not at all? From the size of the error bars I would guess it is the latter.

Zapping Away Depression

This is of course not the only study on mood related use of tDCS.  Since Aldini’s claim of curing Luigi Lanzarini in 1801, tDCS has been studied extensively as a therapy for major depression and bipolar disorder and is used as a last resort clinical therapy.  In this respect there are hundreds of studies and a number of meta-analysis out there.  There are all sorts of variations to the stimulation protocols, electrode configurations, participant selection and measures of self report. In the end however, the results are similar.  There are differences at the group level that often have a statistical probability of p<0.05, but again, have the same confounds and issues of parsing out placebo effects and inter and intra person variability.  One metaanalysis [3] suggests that an N of at least 346 would be required for sufficient confidence.

Factoring in Individual Variation

Relative to 1801, today the hardware is far slicker and the current can be precisely controlled. What appears to fall out of all these studies however, is that the effects are not likely to be uniform from one person to another. Given all the variability in individual brains and variability in mood states and symptoms of depression, one protocol may work for some while different protocols work for others (after all, even the amount of current required to electrocute a person depends on the person).  This means that what might ultimately work are tailored protocols that take into consideration some yet unknown aspect of your unique brain activity. In the end, as it all stands right now, curing 3 out of 12 patients and improving 3 more, as Wiglesworth showed over a century ago, would still be a grand success in psychiatry.

 

[1] The tolerability of transcranial electrical stimulation used across extended periods in a naturalistic context by healthy individuals. Paneri B et al., PeerJ May 2015

[2] Transdermal electrical neuromodulation of the trigeminal sensory nuclear complex improves sleep quality and mood. Boasso A et al, BioRxiv Mar 2016

[3] Transcranial direct current stimulation (tDCS) in the treatment of depression: Systematic review and meta-analysis of efficacy and tolerability.  Meron D et al, Neurosci Biobehav Rev. Jul 2015