Understanding The Mechanism Underlying The Effects of tDCS

The paper, Calcium imaging reveals glial involvement in transcranial direct current stimulation-induced plasticity in mouse brain, is being lauded as a major discovery among tDCS researchers. It is however, extremely hard to follow. Fortunately RIKEN also issued a press release describing the study in a way most tDCS-curious will understand. Read the full press release here.

Researchers at the RIKEN Brain Science Institute in Japan have discovered that the benefits of stimulating the brain with direct current come from its effects on astrocytes — not neurons — in the mouse brain. Published in Nature Communications, the work shows that applying direct current to the head releases synchronized waves of calcium from astrocytes that can reduce depressive symptoms and lead to a general increase in neural plasticity — the ability of neuronal connections to change when we try to learn or form memories.

(top) Low spontaneous calcium activity in a normal mouse followed by tDCS-induced calcium surges. (bottom) tDCS-induced calcium surges are absent in IP3 Receptor 2 knockout mice, indicating that the calcium surges originate in astrocytes, not neurons.
Note: The upper. ‘normal’ mouse brain vs. modified mouse brain, bottom. Watch near ticking clock when ‘spontaneous’ switches to ‘tDCS’.

Let’s put this in some context by having a quick look at astrocytes and glial cells. From 2-Minute Neuroscience

3 thoughts on “Understanding The Mechanism Underlying The Effects of tDCS

  1. This is a pretty dense paper – deep into the details of how neurons and glia signal in the brain. I think some important takeaways have been missed in the press release (and the resulting general discussion on the internets).
    – The authors mainly study glial activity – they see that waves of calcium are evoked somewhat simultaneously (on the order of 10-20 seconds) in response to tDCS. Normally, these glial calcium waves aren’t so coordinated.
    – They don’t observe changes in neuronal calcium activity in the same way. They do, however, see that the glial effect described above is dependent on neurotransmitter signaling (norepinephrine) – which is presumably released from neurons in response to tDCS. They also see a change in the ‘throughput’ of the neuronal response following tDCS, which is also dependent on norepinephrine.

    The bottom line: Neurons and glia are intimately associate, and tDCS is influencing the activity of both types of cells. From my read of it, tDCS may be acting on neuronal elements first, which then induces the glial effects. But more details need to be worked out to show that point conclusively…

    • Thanks Alex! Marom Bikson and Walter Paulus also weigh in on the study in this New Scientist article. It’s definitely got a lot of people thinking. I don’t think we’re any closer to understanding the mechanism for TMS in depression either. I’m sure this also has implications for your work at Tal with LFMS. Best, John

      • Hi John,
        Thanks for the link to the New Scientist article. All the work on tCS, TMS, etc is really important and valuable. I expect we’ll find some common basic mechanisms (like how an electric field affects brain tissue), but then each modality will have its ‘secret sauce.’
        As for how and why any of these approaches are therapeutically beneficial – I expect we’ll have to wait for both the device world and the neuroscience world to take a few steps forward before we get those answers..

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