DC4MND

DC4MND Multidimensional mechanistic investigations of trans-spinal direct current stimulation in Amyotrophic Lateral Sclerosis.

Dear All!Another success of our group! Recently, the next article has been published from the hands of the DC4MND consor...
12/11/2025

Dear All!

Another success of our group!
Recently, the next article has been published from the hands of the DC4MND consortium. This time, we decided to verify whether invasively applied, acute anodal tsDCS will provide significant changes in the spinal motoneurons' electrophysiological properties of SOD1 G93A mice.

Our assumptions turned out to be wrong, and the invasive application didn't cause a significant change in MNs' firing properties. That can be attributed to a rapidly diminishing tsDCS-evoked electric field, as computational modelling showed.

If you are interested in check it out for yourself!
researchgate.net/publication/397520837_Acute_Invasive_Dorso-Ventral_DCS_Applied_With_a_Ball_Electrode_Does_Not_Alter_Spinal_Motoneurons'_Firing_Characteristics_in_the_SOD-1_G93A_Mouse_Model_of_ALS?_tp=eyJjb250ZXh0Ijp7InBhZ2UiOiJwcm9maWxlIiwicHJldmlvdXNQYWdlIjoiaG9tZSIsInBvc2l0aW9uIjoicGFnZUNvbnRlbnQifX0

Best,
Bartek!

Dear All! We are proud to announce that our first paper, entitled “A computational model of tsDCS effects in SOD1 mice: ...
25/09/2025

Dear All!

We are proud to announce that our first paper, entitled “A computational model of tsDCS effects in SOD1 mice: from MRI-based design to validation,” has been published in "Computers in Biology and Medicine", coming straight from the collaborative efforts of the DC4MND consortium members.

This work integrates contributions from multiple teams: starting with high-resolution MRI scans of the mouse model (German Team- Universität Ulm), followed by computational modeling of the animal, tsDCS electrodes, and modeled current spread (Portuguese Team - Instituto de Biofísica e Engenharia Biomédica), and culminating in in vivo validation (Polish Team - AWF Poznań - Akademia Wychowania Fizycznego im. E. Piaseckiego w Poznaniu).

This milestone represents a significant step in our collaborative efforts, and we are excited to share it with the community.

Find the open-access publication at the link below and check it out for yourself!
https://www.sciencedirect.com/science/article/pii/S0010482525014349

Best regards,
Bartek

Hi!  Last time, I explained how the ramp protocol works. However, the most important part -  the MN firing pattern is st...
28/01/2025

Hi!

Last time, I explained how the ramp protocol works. However, the most important part - the MN firing pattern is still unknown to you. As you already know, when the current is injected into the MN during the ramp the voltage becomes less negative (depolarizes), and finally, the cell (if it is capable of it) starts to generate action potentials.
As more and more current is injected, MN firing will start to accelerate and we can actually plot the MN firing frequency (Hz) against the current intensity (nA), to obtain the “I-F curve”.
When MNs are healthy at the beginning of the I-F curve, we can observe a rapid increase in firing frequency, up to a certain point. From this point onwards, this gain of the firing starts to be linear. The first (rapid) part is called the subprimary range of firing, while the second (linear) part, is called the primary firing range (PR). The boundary between these two parts is marked in the figure. As the PR is linear, we can plot a linear regression for this part of the I-F curve and the slope of this regression will give us the idea of the firing ‘gain’. In other words, we will know how fast the MN firing will increase when excitatory input (mimicked by the injected intracellularly current) gets stronger
The above-mentioned firing pattern is characteristic for healthy, MNs, as it is the physiological firing pattern. However, it was shown that in ALS, MNs affected by the disease are not able to exhibit steady-state firing in the PR. Their firing pattern is very chaotic, and almost 50% of cells are not able to generate action potentials repetitively.
As you probably assume, anodal tsDCS has a strong impact on the MN firing pattern! First, it reduces the firing frequency gain (lesser slope of this gain), which agrees with the previously observed changes (decreased plateau and ramp input resistance, and voltage upswing - decreased excitability). However, it also allows more cells to exhibit steady-state firing! So they act more like normal healthy cells! It therefore looks like chronic, anodal tsDCS indeed decreases MN’s excitability, and firing, however, it restores the physiological firing pattern in MNs impaired by ALS.
So that’s the end of our journey with the International Motoneuron Meeting Bordeaux 2024 poster. Stay tuned for more updates, and there's plenty to update!

Hello Everyone!Let’s continue our journey with the poster. Today, we’ll begin discussing the firing properties of spinal...
14/11/2024

Hello Everyone!

Let’s continue our journey with the poster. Today, we’ll begin discussing the firing properties of spinal motoneurons, but first, I need to explain the Ramp protocol. In the top image, you’ll see a blue trace that represents the intracellular current injected in a triangular pattern during this protocol. In the figure below (A), you can observe example responses from two cells—one green (sham) and one orange (anodal)—to this current injection.

As you can see, at the beginning of the current injection, the cells start to depolarize (the voltage becomes more positive) until reaching a specific point (voltage threshold) where they begin to generate action potentials. The current intensity at which the motoneuron begins firing is called Ion.

This voltage change is partially linear, allowing us to plot a linear regression (as shown in Figure B), and the slope of this regression provides the value of the Ramp Input Resistance. Interestingly, this depolarization is technically similar to the plateau input resistance, as both represent a voltage shift evoked by a linear current change. The Ramp IR is also significantly decreased (p

My Dears!  Let’s move today to the most interesting part of the poster, namely the effects of 10-day, 15-minute sessions...
25/09/2024

My Dears!

Let’s move today to the most interesting part of the poster, namely the effects of 10-day, 15-minute sessions of anodal tsDCS on the electrophysiological profile of the lumbar motoneurons of a mouse model of Amyotrophic Lateral Screlorsiss (ALS) - SOD1 G93A. If you’re unfamiliar with the process of chronic tsDCS, the methodology of this part of the JPND Call 2022 project has been presented in a previous post.
Starting with passive membrane properties, the first thing you will notice are 3 traces (green, orange and black), they are related to the first parameters that we examine with the Input Resistance Protocol. During in vivo intracellular recordings, as shown by the black trace, we inject de- and hyperpolarizing pulses of current, and we measure the voltage deflection they evoke at the beginning (Peak) and the end (Plateau) of the pulse. Then the current intensity is plotted against the shift of the voltage, and the SLOPE of this relationship gives us values of the Peak, and Plateau Input Resistance.
As you can see in the boxplots below we only observed a significant decrease in plateau input resistance (p

Hello Everyone!I’d like to present to you all, a poster that was showcased by the Polish team during the International M...
17/09/2024

Hello Everyone!

I’d like to present to you all, a poster that was showcased by the Polish team during the International Motoneuron Meeting in Bordeaux 2024!

But hold on! The data will be shared partially, and each section of the poster will be accompanied by a description and explanation.

All right, let’s get started. As you know from our previous post, the first step of the project was measuring the voltage deflection evoked by the technique, we are examining – tsDCS - in our animal model of Amyotrophic Lateral Sclerosis (ALS), the transgenic SOD-1 G93A mouse. On the poster it was covered under the chapters “Methods #1” and “Results #1”.
If you want to learn more about this step, check our previous data 😉.

The Portuguese team, by combining our results with high-resolution MRI scans of the mouse spinal cord, was able to define the current intensity, that mimics the one used in humans, which is 60µA. With that knowledge, we were able to move on to the next phase of the JPND Call 2022 project.

Now, let me tell you about the second part, starting with “Methods #2.”

In the second part of the project, we needed to verify the impact of chronic and acute tsDCS on the firing properties of spinal cord motoneurons. The Polish team was tasked with determining the effect of chronic tsDCS. So how was this done methodologically?
For 10 consecutive days, we anesthetized the animals with harmless isoflurane. The animals in the “Anodal” group were polarized for 15 minutes, with the current intensity mentioned earlier. Meanwhile, the animals in the “Sham-Control” group were also anesthetized, and the tsDCS electrodes were also placed on their backs, but no current was passed. This procedure was essential to rule out any influence of isoflurane anaesthesia on the motoneuron electrophysiological profile. On the 11th day, so the day after the last tsDCS session, in vivo, intracellular recordings of spinal motoneurons were made.
Alright, that’s it for now, we will start discussing the results in another post!

Hello Everyone! Last week, an official DC4MND consortium meeting took place. During it, especially young members of all ...
31/05/2024

Hello Everyone!

Last week, an official DC4MND consortium meeting took place. During it, especially young members of all teams (Germany, France, Portugal, Latvia, Italy, and Poland) presented the results obtained by each team during the 1st year of the project. Due to various responsibilities, not all members were able to attend in Poznan, however, the Portuguese and French teams visited us in person 😊.
It was a full day of fiery presentations, discussions, and collaborative planning of further steps. Each team had made tremendous strides in the project, and the meeting only fueled everyone with new ideas and drove them to further work.
We have also showcased the Portuguese team's electrophysiological laboratory, particularly the electrodes used for tsDCS and we have conducted an experiment to demonstrate the real setup of tsDCS stuff. That allowed our partners to gather the most crucial and necessary information for their biophysical measurements of current spread and for creating the best in vivo and in vitro computational model.

Looking forward to hearing what you think. Have a great day!
Bartek

Hey everybody!Today I’m going to share the first results of our experiments! Let's start from the beginning.To start our...
26/05/2024

Hey everybody!

Today I’m going to share the first results of our experiments! Let's start from the beginning.

To start our experiments with trans–spinal direct current stimulation and to be as precise as possible, we had to define how the direct current spread through the tissues.

To do that, as in the previous post described, two electrodes were placed on the skin of the back in a rostrocaudal arrangement, and then a painless, direct current of different intensities was passed. To establish the DC spread, we measured the deflection of voltage in the spinal cord at the onset of the DC application. Moreover, we measured the distance from the rostral ("active") electrode to the recording site.

Below on the graphs, we plotted the voltage deflection vs. the distance from the active (rostral) electrode.
“Dorsal”, “Intermediate” and “Ventral” describe the depth of our measurements. For dorsal horns, the depth was about 300 μm, for intermediate about 1000 μm, and for ventral horns about 1400 μm. “Anodal” and “Cathodal” describe the type of current that was passed, and the last one is the value of current intensity. We performed our experiments with current with intensity 10 and 100 μA.

Interestingly our experiments show that the farther away from the active electrode we are, the amplitude of the deflection decreases, and if we move close to the opposite electrode, then the deflection moves in the opposite direction! So, if we apply anodal (depolarizing) current, then we will have spinal depolarization close to the rostral electrode and spinal hyperpolarization close to the caudal electrode. Remember that the wave of depolarization is what facilitates the activation of motoneurons!
Our innovative findings have been sent to our partner from Instituto de Biofisica e Engenharia Biomedica in Lisbon, where they will be created computer models of direct current spreading.
I’m looking forward to your feedback!
Bartek

Hello Everyone!Last posts were about our project, trans–spinal direct current stimulation basics, and how tsDCS works. T...
20/12/2023

Hello Everyone!
Last posts were about our project, trans–spinal direct current stimulation basics, and how tsDCS works. Today I’d like to introduce you to the basics of electrophysiology.
So, from the beginning…
Motoneurons are specific nerve cells that connect to the muscle fibers. These connections allow us to perform all movements, however, it is possible only because motoneurons are excitable, so they respond to stimuli and generate action potentials.
Excitability is the result of the presence of resting membrane potential. But what is it?
Resting membrane potential (RMP) is a potential that is present due to differences in the distribution of positively and negatively charged ions such as sodium, potassium, calcium, chlorine, and others between the two sides of the cell membrane. This difference oscillates around the -70 millivolts (mV) but may vary from cell to cell. The fact that the difference is negative, indicates that the interior of the cell holds more negative ions while the extracellular space holds more positive ions.
So we know now that the cell is polarized. But more is needed to generate action potential. The cell also needs to have some way to respond to stimuli and rapidly change the polarization level. After all, the nerve signal is actually a propagating wave of changing potential. However, what enables this signal to occur and propagate?
The answer is - ion channels! Ion channels are specific types of trans-membrane proteins, which are voltage-gated and allow ions to flow from one side of the membrane to the other. Voltage-gated means that, at rest, the channels are closed, but in response to small changes of potential they can open up and cause a sudden influx of ions (mainly Na+). The influx of positively charged ions will cause “depolarization” that is, a change in potential to a more positive one. This wave of depolarization will then travel the motor nerve and initiate muscle contraction
However, it is not all about generating the action potential!
The whole process is a bit more complicated, but don’t worry in the next post I will explain it to you from A to Z 🙂.
Bartek
(In the figures below you can see the differences in ions distribution, and in the second an example of an ion channel Source: Principles of Neural Science. Eric R. Kandel, James H. Schwartz, Thomas M. Jessell).

Bartek

Hello everyoneToday briefly about trans - spinal direct current stimulation. What is it, how it works and more.Trans - s...
15/11/2023

Hello everyone

Today briefly about trans - spinal direct current stimulation. What is it, how it works and more.

Trans - spinal direct current stimulation (tsDCS) is a unique, non-invasive and constantly developing neuromodulation technique that allows safe, painless and cost - efficient treatment of several neurodegenerative diseases including Amyotrophic Lateral Sclerosis (ALS).

To date various conditions such as hereditary spastic paraplegia, restless leg syndrome, incomplete spinal cord injury and chronic pain have been successfully treated with trans - spinal direct current stimulation.

During the procedure, two electrodes are placed on the skin of the back and then a painless, low-intensity direct current is passed.
In this arrangement, we can carry out both anodal and cathodal polarization.
In a nutshell, our previous studies have shown that anodal polarization makes motoneurons more depolarized, which facilitates and increases the effectiveness of their activity.
The cathodal current, on the other hand, has the opposite effect and moreover, its divergence is not so clear-cut, as our first study shows.

Therefore, in the DC4MND project, we decided to conduct our polarization experiments with anodal current, which seems to be more effective.
Our first results confirm the reports of previous studies

In future posts, we will present you with more details and more specific data related to trans - spinal direct current stimulation effects on motoneurons.

That's it for today, stay tuned for more information coming soon!

Bartek

(In the photo, our brave patient during tsDCS session😉)

04/11/2023

Hello everyone!

I am extremely glad that you have visited our profile!

DC4MND is a project carried out under the scope of The EU Joint Programme – Neurodegenerative Disease Research (JPND) is the largest global research initiative aimed at tackling the challenge of neurodegenerative diseases. We bring together young and experienced, female and male respected scientists from Poland, Germany, France, Italy, Portugal and Latvia to unravel the mechanism behind the protective actions of trans-spinal direct current stimulation (tsDCS) in ALS.

Our consortium incorporates specialists in electrophysiology, mathematical modelling, bioinformatics, molecular and cell biology and genetics, which allows for an unprecedented holistic approach to tackling the project objectives.

We invite everyone interested in ALS management: Scientists, Clinical Neurophysiologists and in particular Patients and Patient associations to like our profile to get the latest updates.

In future posts among others we will present what trans–spinal direct current stimulation is, how it works, what effects of tsDCS has been described so far and its significance in ALS therapy.
We encourage everyone interested to check out the project fact sheet:
https://neurodegenerationresearch.eu/wp-content/uploads/2023/05/DC4MND-Project-Fact-Sheet.pdf

That's it for now, more details coming soon!

Bartek

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