Transcranial Direct Current Stimulation

Epistemic status: rough-draft, I wouldn’t be surprised if my conclusions reversed

tDCS consists of a pair of sponge electrodes on the head, through which constant current is placed, at about 0.029-0.08 mA per square centimeter. Locations vary based on the intended effect of the treatment.  Extending treatment is usually done by prolonging duration rather than increasing intensity, as higher currents cause more cutaneous pain. When done correctly, the stimulation is painless, and therefore can be compared to sham stimulation as a control.[1]

Bottom lines: there are some serious methodological flaws in tCDS studies.  “Sham” stimulation isn’t a perfect control, so some significant proportion of the effect may be placebo. And there’s quite significant variation in how much a given application of current increases the evoked potential in the brain.  Also, almost all the studies are quite small.

Given that, though, the effect sizes on working memory are quite good — comparable or better to the best nootropics (caffeine, modafinil, and amphetamine.)

As a treatment for depression, tCDS looks less impressive; aggregating the best-quality studies gives no net effect compared to sham stimulation.

As a treatment for chronic pain, tCDS looks quite good, though there’s not very many studies.

Cognition

A study of 15 healthy females found a slight improvement on a working memory task from anodal stimulation to the DLPFC, but not from cathodal stimulation of the DLPFC, stimulation of M1, or sham stimulation.  Cohen’s d is 0.66. [2]

18 patients with Parkinson’s given 1-2 mA of tCDS to the DLPFC for 20 min found a 20% increase in correct answers on a 3-back task compared to sham stimulation for 2 mA.  Stimulation with 1 mA improved accuracy by only 5%. Stimulation of M1 had a significant improvement of reaction time but not accuracy. Cohen’s d is 3.5.[3]

32 patients given sham, anodal, or cathodal stimulation of the DLPFC or M1 found that accuracy on a word-memorization task was significantly better with anodal DLPFC stimulation than sham (88% correct vs. 80% correct), while cathodal stimulation was worse than sham.  Sham and M1 stimulation were similar.  Cohen’s d was 3.5. [7]

18 subjects given a verbal-associative task with anodal DLPFC tCDS vs sham or cathodal tCDS significantly improved mean scores (9 vs. 7 out of 12 correct). There was no effect on verbal fluency scores (a test of how many unique words one can produce in a short timespan).  Cohen’s d was 0.8.[8]

12 patients given a 2-back task with sham, anodal DLPFC tCDS, or transcranial random noise stimulation found a significant improvement in speed but not accuracy for 2-back anodal tCDS vs. sham.  Cohen’s d was 0 for accuracy, 0.36 for speed.[9]

10 Alzheimer’s patients treated with tCDS on the DLPFC and left temporal cortex found significantly more correct responses with tCDS vs sham on a memorization task (30 vs. 35 correct responses out of 55) but no improvement in Stroop or digit span tests.  Cohen’s d was 1.[12]

16 Parkinson’s patients given tCDS to the DLPFC significantly improved phonemic verbal fluency relative to sham and TPC stimulation (p < 0.002) but did not improve semantic verbal fluency.[17]

In a study of 12 healthy subjects given a naming task, reaction times were decreased with anodal tCDS to the DLPFC and increased with cathodal tCDS to the DLPFC.[18]

15 healthy subjects given a 3-back working memory task given anodal tCDS to the DLPFC significantly improved accuracy with tCDS vs sham (80% correct vs 69% correct).  Cohen’s d of 0.87.[18]

10 stroke patients given a 2-back working memory task, treated with anodal DLPFC tCDS or sham, found significant improvement in accuracy in anodal but not sham groups. Cohen’s d of 2.4.[19]

28 patients with major depression given a 2-back task given tCDS or sham on the DLPFC found a significant improvement in accuracy with the active version vs. sham: 58% vs 42% correct, p = 0.04, Cohen’s d about 4.[20]

58 healthy subjects given working memory training had an effect size of DLPFC tCDS vs. sham of 1.5 on digit span (p = 0.025) , 1.35 for Stroop accuracy, 1.3 on the CVLT, no effect on Raven’s.[21]

30 healthy older adults were given sham or real anodal tCDS to the left DLPFC and given a 3-back test; there was no significant effect of stimulation on working memory performance.[24]

37 patients with temporal lobe epilepsy had no improvement in working or episodic memory from anodal tCDS to the left DLPFC.[25]

Mean Cohen’s d for working memory accuracy, weighted by sample size: 1.5.

A meta-analysis of 16 studies of anodal DLPFC tCDS found a mean effect size of 0.14 for accuracy and 0.15 for reaction time.[22]

I’m not certain why I’m getting such different numbers, except that my “review” seems to have included different studies than the meta-analysis did.  If you averaged the results, you’d still get a mean effect size of 0.75, which corresponds to a strong effect.

Speech

10 aphasic stroke patients treated with anodal tCDS over Wernicke’s area vs. sham: significantly improved accuracy on a picture-naming task (40% vs 20% correct before training, and 70% vs 50% after training.)  Anodal tCDS also improved mean reaction time (1.8 sec vs 2.5 sec.)  The improvement persisted 3 weeks after treatment.[6]

In 10 healthy subjects, anodal tCDS over Broca’s area vs sham increased verbal fluency: mean number of words were 22 vs. 16, and mean number of syllables was 15 vs. 14.  There was no effect when the tCDS was switched to the right-hemisphere analogue of Broca’s area.[10]

Pain

A study of 17 patients with central pain due to traumatic spinal cord injury, given 2 mA of tCDS to the motor cortex M1 or sham tCDS found a significant improvement of pain scores — from a 7 (out of 9) to a 4.  The effects of consecutive sessions were cumulative.  There was no significant effect of treatment on anxiety or cognitive function.

32 female patients with fibromyalgia were treated with sham tCDS, tCDS of M1, or tCDS of the DLPFC.  M1 stimulation worked, sham and DLPFC did not. Out of a subjective improvement scale (where 2 is “much improvement”,  3 is “minimal improvement”, and 4 is “no change”, the group treated with M1 tCDS was at 2.5 and the sham group was at 3.5; the DLPFC group was at 3.  This was 2 mA, 20 min/day, for 5 days.[4]

41 female patients with fibromyalgia treated with tCDS on M1, DLPFC, or sham found that M1 stimulation significantly improved pain scores compared to DLPFC or sham: from about a 6 (which was baseline) to a 4.  No significant effect on depression scores.[11]

A meta-analysis of tCDS for chronic pain found a pooled effect size of 2.29 on pain symptoms.[23]

Depression

A meta-analysis of the use of tCDS in depression (directed to the DLPFC) found that the mean effect on depressive symptoms was significant: a Hedges’ g score of 0.743, significant at a p-value of 0.006. There’s a bit of a bias in the data: the Fregni and Boggio labs had significantly larger effect sizes than the other labs, and there was significant heterogeneity in results. Only a minority of patients (10-30%) were responders.  The average reduction in symptom severity was about 30%.[5]

Another meta-analysis of 6 RCTs of tCDS in depression found no significant effect of tCDS vs. sham on response rates or remission rates for depression.[13]

Blinding issues

There are more frequent reports of itching and burning with real than sham tCDS, suggesting that blinding may not be sufficient.[14]  Participants are able to guess more accurately than chance whether they are in the active or sham treatment.[15]

Other problems

The MEP (electrical activity change) due to tCDS is extremely variable both between individuals and within the same individual. The MEP effect of tCDS can be abolished by moving or thinking while the current is being administered.[16]

DIY

If you want to zap your brain, there are a variety of places that sell tCDS devices.

The Brain Stimulator is $59.95

The foc.us  stimulator is $249, plus headsets and cables.

The Apex is $139.99

The Fisher Wallace Stimulator is $699.

Soterix Medical makes the standard clinical-use device, for investigational use only.

And, of course, a lot of people make DIY versions.

Safety issue to keep in mind: high voltage to your brain is not good. Anything above 2 mA is outside the range of what’s been studied and probably a bad idea.  If it hurts your skin, it’s too strong. A TENS unit is too strong.  A 9-volt battery is too strong. Do not do the thing.

References

[1]Nitsche, Michael A., et al. “Transcranial direct current stimulation: state of the art 2008.” Brain stimulation 1.3 (2008): 206-223.

[2]Fregni, Felipe, et al. “Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory.” Experimental brain research 166.1 (2005): 23-30.

[3]Boggio, Paulo S., et al. “Effects of transcranial direct current stimulation on working memory in patients with Parkinson’s disease.” Journal of the neurological sciences 249.1 (2006): 31-38.

[4]Fregni, Felipe, et al. “A randomized, sham‐controlled, proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia.” Arthritis & Rheumatism 54.12 (2006): 3988-3998.

[5]Kalu, U. G., et al. “Transcranial direct current stimulation in the treatment of major depression: a meta-analysis.” Psychological medicine 42.09 (2012): 1791-1800.

[6]Fiori, Valentina, et al. “Transcranial direct current stimulation improves word retrieval in healthy and nonfluent aphasic subjects.” Journal of Cognitive Neuroscience 23.9 (2011): 2309-2323.

[7]Javadi, Amir Homayoun, and Vincent Walsh. “Transcranial direct current stimulation (tDCS) of the left dorsolateral prefrontal cortex modulates declarative memory.” Brain stimulation 5.3 (2012): 231-241.

[8]Cerruti, Carlo, and Gottfried Schlaug. “Anodal transcranial direct current stimulation of the prefrontal cortex enhances complex verbal associative thought.” Journal of Cognitive Neuroscience 21.10 (2009): 1980-1987.

[9]Mulquiney, Paul G., et al. “Improving working memory: exploring the effect of transcranial random noise stimulation and transcranial direct current stimulation on the dorsolateral prefrontal cortex.” Clinical Neurophysiology 122.12 (2011): 2384-2389.

[10]Cattaneo, Z., A. Pisoni, and C. Papagno. “Transcranial direct current stimulation over Broca’s region improves phonemic and semantic fluency in healthy individuals.” Neuroscience 183 (2011): 64-70.

[11]Valle, Angela, et al. “Efficacy of anodal transcranial direct current stimulation (tDCS) for the treatment of fibromyalgia: results of a randomized, sham-controlled longitudinal clinical trial.” Journal of pain management 2.3 (2009): 353.

[12]Boggio, Paulo S., et al. “Temporal cortex direct current stimulation enhances performance on a visual recognition memory task in Alzheimer disease.” Journal of Neurology, Neurosurgery & Psychiatry 80.4 (2009): 444-447.

[13]Berlim, Marcelo T., Frederique Van den Eynde, and Z. Jeff Daskalakis. “Clinical utility of transcranial direct current stimulation (tDCS) for treating major depression: a systematic review and meta-analysis of randomized, double-blind and sham-controlled trials.” Journal of psychiatric research 47.1 (2013): 1-7.

[14]Kessler, Sudha Kilaru, et al. “Differences in the experience of active and sham transcranial direct current stimulation.” Brain stimulation 5.2 (2012): 155-162.

[15]O’connell, Neil E., et al. “Rethinking clinical trials of transcranial direct current stimulation: participant and assessor blinding is inadequate at intensities of 2mA.” PloS one 7.10 (2012): e47514.

[16]Horvath, Jared Cooney, Olivia Carter, and Jason D. Forte. “Transcranial direct current stimulation: five important issues we aren’t discussing (but probably should be).” Frontiers in systems neuroscience 8 (2014): 2.

[17]Pereira, Joana B., et al. “Modulation of verbal fluency networks by transcranial direct current stimulation (tDCS) in Parkinson’s disease.” Brain stimulation 6.1 (2013): 16-24.

[18]Ohn, Suk Hoon, et al. “Time-dependent effect of transcranial direct current stimulation on the enhancement of working memory.” Neuroreport 19.1 (2008): 43-47.

[19]Jo, Jung Mi, et al. “Enhancing the working memory of stroke patients using tDCS.” American Journal of Physical Medicine & Rehabilitation 88.5 (2009): 404-409.

[20]Oliveira, Janaina F., et al. “Acute working memory improvement after tDCS in antidepressant-free patients with major depressive disorder.” Neuroscience letters 537 (2013): 60-64.

[21]Richmond, Lauren L., et al. “Transcranial direct current stimulation enhances verbal working memory training performance over time and near transfer outcomes.” Journal of Cognitive Neuroscience (2014).

[22]Hill, Aron T., Paul B. Fitzgerald, and Kate E. Hoy. “Effects of anodal transcranial direct current stimulation on working memory: a systematic review and meta-analysis of findings from healthy and neuropsychiatric populations.” Brain stimulation 9.2 (2016): 197-208.

[23]Luedtke, Kerstin, et al. “Transcranial direct current stimulation for the reduction of clinical and experimentally induced pain: a systematic review and meta-analysis.” The Clinical journal of pain 28.5 (2012): 452-461.

[24]Nilsson, Jonna, Alexander V. Lebedev, and Martin Lövdén. “No significant effect of prefrontal tDCS on working memory performance in older adults.” Frontiers in aging neuroscience 7 (2015).

[25]Liu, Anli, et al. “Exploring the efficacy of a 5-day course of transcranial direct current stimulation (TDCS) on depression and memory function in patients with well-controlled temporal lobe epilepsy.” Epilepsy & Behavior 55 (2016): 11-20.

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