Limits and Research

Limits

The focus is on HD-TES, as it's the most used technique in research at the moment. Although compared to TES there are several improvements, there are still many things to consider:

• understanding how much voltage is actually flowing: each brain region has a unique electrical resistance influenced by its surrounding tissue, complicating precise voltage delivery. Therefore,  surrounding an anode will have a different influence on all the cathodes, concurrent resistance monitoring becomes unreliable (due to varying tissue properties and interdependence of electrodes). 

• We have no knowledge or control on what second area will also be activated or inhibited. This is because every area of the brain is connected directly with many others by neural networks. Therefore, we can't always be sure of what areas are responsible for the behavioral changes of the subject.

• Difficulty in precise stimulation: Current dispersion remains an obstacle, reducing precision and causing unintended stimulation in adjacent areas.

In the image below, white arrows indicate the target and show its Median energy |E| and QCD (quartile coefficient of dispersion)[2]. Red arrows indicate the location and magnitude of the maximum (over the vertices) “Median |E|”. The median TMS EFs are normalized so that the maximum median value equals one. 

How to improve? 

This section consists of my discussions with ChatGPT about whether it might be possible in the future to improve TMS and whether these ideas have already been tried.  

What happens if we increase current in TES?

When we increase the current, it can lead to several adverse effects, such as:

- Increased heating of tissue: As current increases, so does the heat, in the skin and tissues under the electrodes, which can cause discomfort, pain, or even tissue damage. A way to prevent this could be to add more cooling gels. 

- Non-specific stimulation: Increasing the current tends to cause widespread activation, not just in the target area but also in nearby areas, leading to unintended effects like dizziness, headaches, or muscle twitches. However, these side effects can be reduced with High Definition-tES (adjusting electrode dimensions to better match individual brain structures might reduce the spread of current to unintended areas)

- Indiscriminate excitation/inhibition: High current can over-stimulate neurons, leading to unpredictable changes in brain excitability (e.g., paradoxical effects like over-excitation or unintended inhibition). 

- Current steering: Another approach is to use multiple electrode pairs to “steer” the current toward the desired brain region. This involves adjusting the intensity and polarity of current at different electrode sites to focus the electric field on the target area. By shifting the relative intensity between multiple electrodes, one can concentrate current in a deep or localized region of the brain without the need for increasing the total applied current significantly. Until now this has mostly been used for DBS and TMS. Also, they can be manipulated so that the sum strengthens certain areas and cancel each other out in others. 

How could I better target an area? 

• Personalised targeting: Refine electrode positioning using more advanced neuronavigation techniques (like MRI-based targeting), which would help ensure the current is more precisely focused on the intended brain areas. This is already done with TMS, ohere ften an MRI scan is done before, so that one can better target an area when applying the coil. 

• Computational models: The addition of computational models of current flow help predict and optimise TDCS effects, as it allows researchers to optimize electrode placement for specific regions of the brain, improving current penetration, depth and accuracy. 

What about in lying studies? 

Further studies should try to stimulate precisely multiple regions of the brain rather than targeting a single area. For example with Dual site stimulation. Also, it would be necessary to target diverse and precise subregions within the prefrontal cortex. By targeting two brain areas simultaneously, researchers can explore the functional connections between regions, study brain network dynamics, or develop new treatments for neurological disorders.

The key areas found until now:

-     Anterior Prefrontal Cortex (aPFC) critical for moral reasoning and deception. 

-  Temporal lobes: social cognition and understanding of the implications of lying 

-   Parietal cortex: integrating sensory information during deception 

Selective ion channel manipulation to increase ion flow?

The idea is to modulate ion channels to enhance or inhibit the effect of tES in very specific areas (as the current flow works due to the ion potentials). 

• Ion channel agonists/activators: Administering drugs that specifically open certain ion channels in the target brain region could increase ion conductance. For example, sodium channel agonists could make neurons in a specific area more excitable, enhancing the depolarizing effects of anodal stimulation. 

• Ion channel inhibitors: potassium channel activators could enhance the hyperpolarizing effects of cathodal stimulation, making neurons less likely to fire.

This could also be achieved via: 

- light sensitive drugs (that respond to a specific wavelength) 

- electromagnetic activated drug (respond to magnetic fields, One major challenge with magnetogenetics is that weak magnetic fields do not produce strong enough responses for practical use, while stronger fields might have unintended effects on other tissues)

- ultrasound (a noninvasive technique that can target deep brain regions (like in a liposome or nanoparticles  and opens up only in target area)  

For more information on current research, check out the ETH Zürich lab on how they created a Flexible tentacle electrode, that precisely record brain activity!