1) What is your experience with temporal interference (a la Ed Boyden; Grossman et al., Cell, 2017) for targeting?
The promise of temporal interference stimulation is non-invasive targeting of deep structures. A few things to keep in mind. We’ve know for a while that even regular pad-tDCS goes deep (PMID: 22512348), much deeper then many techniques called “deep”, but superficial regions are also activated. Hirata and colleagues recently showed regular tDCS can even be “reliable” to deep regions (PMID: 31839398). So its proving something is special in going deep, we need to show superficial regions are spared. There are various ways to optimize deep current flow using multiple electrodes, my colleagues Lucas Parra did a nice job contrasting them (PMID: 30297323). My own labs recent work has focused on oscillations, and we proposed that if temporal interference stimulation can be translated to human it may depend on both the sensitivity and selectivity provided by brain oscillations ( https://www.biorxiv.org/content/10.1101/2019.12.25.888412v1
). Zeinab Esmaeilpour from my lab does a great job of explaining this work her https://youtu.be/_jqB3Dx0w6Q?t=5140
2) Hi, I want ask if there is any differences between 4*1 electrodes and concentric ring electrodes? Thank you. Hanna from Hong Kong.
In 2008, when we first though of focal transcranial electrical stimulation, using a sphere model we proposed using a small center electrode surrounding by a single ring electrode (PMID: 18441418). When we developed the first MRI derived models, we tested replacing the single ring electrode with 4 smaller “HD” electrodes (PMID: 20648973). So we can this “4x1”. It can be challenging (messy) to practically set ups large circle electrode (e.g. prevent gel smearing between the center and cycle electrode) while HD electrodes are very reliable to set up, not to mention comparable with EEG and other techniques. It may be that sometimes we call the 4x1 HD-tDCS month a concentric ring montage, and that can be confusing. Incidentally, this paper explains why 4 is the Goldy Locks number (PMID: 27223853)
3) As it was shown the tES stimulates the active neurons, so, does it means, for a better result tES should be applied together with a therapy that works with those neurons?
I can say that based on experiments in brain slice, we see that slicing neurons (at rest) will not be driven to fire by low-intensity (~1 V/m) electric fields. Only neurons that are close to fire, or about to fire, get modulated by weak tES. We and others showed this the single neuron (PMID: 17947123) and oscillations levels (PMID: 21068312; PMID: 20624597). And as I explained, we think only system already undergoing plasticity will be boosted, "tDCS is Hebb” (PMID: 31668982). So based on this, yes, tES should be applied together with therapy. BUT, the brain slice is not a complete system, for example lacking active blood supply which I think is a target of tDCS (PMID: 29915178). Also, brain slices are dead quiet when not otherwise activated by the intact brain is always active, so there is always “something going on” that can be modulated by tDCS (PMID: 21962981).
4) As we also have been seen we are moving to a more personalized Therapies, which requires Closed-Loop (with EEG, or as shown TMS tgether with tES and the need of Neuronavigator to place the electrodes and coils.. This makes more difficult the Home-use of tES. What is in your opinion the future of Home-use tD-tES?
In principle, providing patients the access, comfort, respect etc. of therapy at home when possible is important. tDCS can go home, provided - and only provided- the right steps are taken to “flatten’ risk and ensure reproducibility. I think the Remote Supervised approach is one systematic and validated way to do this (PMID: 25852494). I think new technical approaches, such as closed-loop stimulation, can be developed at clinical and academic centers. Often when a technique is then modified to be deployed at home, designers need to make intelligent decisions to maintain robustness. I think its a mistake to take closed-loop (just as with open loop) tES systems designed for laboratory use, and expect reproducible outcomes under home use. I see a future when home used tES and brain monitoring are as ubiquitous as drugs, but its up to researchers and engineers to do solid work to get us there.
5) Would expect that synapses closer to the surface of the brain (L1? L2/3?) would be more affected than deeper layers?
I’m not sure about that. The current density (or electric field) does not change much as one moves from superficial to deep grey matter (PMID: 23478132). Actually the fact the the electric field does NOT change quickly over space is the basis of the "quasi-uniform assumption" which underpins all computational current flow models of tES and all animal models of tES (PMID: 27693941, PMID: 23290681). For me the quasi-uniform assumption seems the most widely applied yet never mention assumption in tES research,
6) What is the state-of-the-art for tACS in the elderly?
I’d consult papers modeling how brain current flow is impacted by age such as this monumental effort by Adam Woods and colleagues (relevant for tACS and well as tDCS) (PMID: 32289695). Dr. Woods is also leading among the largest (if not the largest) trials on tDCS in aging "Augmenting Cognitive Training in Older Adults (The ACT Study)”. So I’m excited for increasingly pivotal trials on tDCS in aging, and I expect tACS applications will develop alongside these.