The Future of tACS

This post is the result of thoughts fermenting in my mind for the last few months. As you may know, one area the Frohlich Lab focuses on is the use of non-invasive brain stimulation to engage and modulate brain rhythms (transcranial alternating current stimulation, tACS). Six years ago when we started the Frohlich Lab, this was a quite unusual idea and only few others were pursuing this approach. Today, a lot of research effort is going in that direction. Yet, more critical voices have started to emerge and I feel it is time to begin mapping out my own thought process on the future of tACS. I am focusing on tACS and not tDCS since I know much less about tDCS. In no particular order:

• We are reaching data lock for our first two tACS treatment clinical trials (schizophrenia and depression) in the next few months. To my knowledge, we are the first ones to do such studies in psychiatric populations (if not, please let me know, my impression is derived from searching clinicaltrials.gov). Will the results define the future of tACS as a treatment? Clearly no - they are small pilot studies with (almost) all limitations of small studies (few tens of participants). Also, we started these studies when we knew much less about target engagement by tACS. Will the media try to overhype the results (especially if positive). Clearly yes. So buckle up, this will get crazy. As a preview: we have some patients who got dramatically better. All placebo? Maybe!
• Overall, the number of attempts to reproduce tACS results (including ours) is as close to zero as it can be. Please let me know if you can point me to a clean and clearly reproduced tACS result (two different research groups!).
• We all know/suspect that at least half of the tACS studies undertaken are negative - where are the published reports??? If this field is supposed to survive (which I hope it will for the benefit of patients) everybody needs to publish their negative findings. If no journal takes the paper (shame on the journal!) then put it on a preprint server or something. Please!
• The number of tACS studies with proper EEG (even just before and after stimulation) is still frustratingly low. Can the basic findings of modulating alpha oscillations be reproduced? We need to know. The Frohlich Lab is working on this but ideally at least ten other labs are willing to try. All it takes is 20 healthy controls, a basic EEG, and a brain stimulator!
• Successful blinding. Blinding tACS interventions is very difficult due to the phosphene issue (light perception triggered by stimulation of optical nerve). We as a community should do much better in addressing this and in trying to establish reasonable solutions. As a first step, please publish your blinding stats such that we know if you have successfully blinded your participants and device operators.
• We still need much more work on target engagement - we have converged on the Arnold tongue as potential mechanism but even that has yet to be demonstrated in vivo! There is a tremendous need for more preclinical work and computational neuroscience studies to better elucidate if and how tACS engages network oscillations. We are very grateful to NIMH and the BRAIN initiative to support our efforts in the realm of tACS for targeting thalamo-cortical rhythms, in particular the alpha oscillation. Much more of this is needed!

Please give these points some thought and let me know if you agree/disagree/have other points to add. This is crucial. I am convinced that tACS can morph into a successful neuroscience tool and also therapeutic intervention. But we need to be smart and collaborate. Let me know if you have any questions - I am always happy to discuss/help. My only conflict is that I may recommend XCSITE 100 from Pulvinar Neuro - not because I make significant/any money with it (far too small of a business - we exist to enable high quality research)- but because I think effective blinding and quality control are essential for successful research!