Posts Tagged tACS
At Neuroelectrics, we believe in the advantages and effectiveness of transcranial electric stimulation (tES) in treating numerous brain diseases. Yet, despite the increasing number of tES publications per year, the lion’s share in the market of non-invasive brain stimulation technologies is still played by transcranial magnetic stimulation (TMS), likely because TMS received US-FDA approval in 2008 whereas tES has not yet.
Does this mean TMS is more effective? Well, it’s not quite fair to say so, considering TMS studies started at least 10 years earlier than those of tES. Therefore, there are several more clinical trials proving TMS efficacy.
However, the two techniques are close relatives: you can think of TMS as the elderly, stiff and sturdy brother, and tES as the younger, more flexible and easy-going one.
In this blogpost, we’ll go over the roots of their differences and see when and why you might prefer one over the other.
[E-fields patterns and biophysical substrates]
At a fundamental level, the two techniques rely on different physics and induce distinct patterns of electric fields (E-field) on the cortex, acting on a different neural substrate.
TMS is based on electromagnetic induction: a large magnetic coil is placed just a few centimetres above the scalp to stimulate over a specific cortical area. When the operator launches the electric pulse, vast amounts of current flows suddenly through the coil and creates a magnetic field around it, which varies rapidly in time. This changing magnetic field induces a very short (order of 1ms), highly localized (figure 1), super-threshold (order of 100V/m) E-field in the cortex. The E-field maximum is reached on the gyrus right under the coil, and the orientation is mostly parallel to the cortical surface.
The most sensitive cells to an E-field with such characteristics are interneurons and collaterals of pyramidal cells aligned tangentially to the cortical surface, which are automatically triggered to fire.
Instead, tES operates in the (quasi-)static regime, as only a small amount of direct current (DC) or low frequency alternating current (AC) is applied through electrodes placed directly on the scalp. The temporal resolution of the technique is low because the neuromodulatory effects begins a few seconds after the start of stimulation. Moreover, the E-field generated is much weaker (order of 0.1V/m) and less focalized (although the focality can be improved by using multichannel montages, it remains much lower than TMS E-field). Depending on the electrodes’ geometry, the maxima can occur on the gyri at the edges of the electrodes or between them. The overall orientation of the E-field is normal to the cortical surface, which indicates that tES probably influences layer V pyramidal neurons, as they are mostly perpendicular to the cortex.
Given the low, subthreshold intensity, the tES E-field cannot cause neural firing, but it is able to modulate the firing rate, facilitating or inhibiting the activation of pyramidal cells.
Other important differences concerning system setup.
TMS technology is more complex and cumbersome. The cost of the whole equipment is between 50-100k USD or Euros. This includes a wall-powered and heavy stimulator about the size of a fridge, a coil connected to the stimulator by a high-voltage cable, a mechanical arm to hold it in place, and a neuro-navigation system to accurately place the coil over the target brain region. The coil hangs suspended over the head of the patient, and since the strength of the effects depends on the coil-cortex distance, it’s crucial to keep it at the specific distance. For this, during the treatment session, the patient must sit still in a specially designed chair, with positioning frames around the chin and forehead.
On the contrary, tES is much cheaper and effortless: the cost is between an average of 6-30k USD/Euros, and the whole setup fits a shoe box. The stimulator can be as small as a mobile phone, light/portable, and almost always battery powered. The electrodes are directly in contact with the scalp, held in place by a rubber band or a neoprene cap. This way, the patient can move and even walk during the stimulation session.
Despite the underlying differences, TMS and tES are both quite versatile tools for treatment and research, and they offer similar options.
In research settings, you can leverage on TMS’ high spatial and temporal resolution to study how brain networks dynamically operate. In this context, TMS is usually performed online (during task performance) by applying one pulse at the onset of a stimulus (single-pulse TMS), or two pulses over separate regions which are interconnected (paired-pulses TMS). But tES too allows one to study the causal link between cortical areas. For instance, with tACS, one can simultaneously apply oscillatory currents over distinct regions at the same frequency but with different phases to promote or hamper the synchronization of functional networks.
Clinical applications of brain stimulation techniques instead tend to focus more on long-term effects, promoting network neuroplasticity that can outlast the period of stimulation.
In this case, TMS is usually ran in the repetitive mode (rTMS), which consists in multiple pulses within just microseconds. Frequency lower than 1Hz has been linked to long term depression (LTD), whereas frequency above 5Hz to long term potentiation (LTP). Similar outcomes can be achieved with tCS using either tDCS anodal or cathodal stimulation, which has been shown promoting and inhibiting synaptic activation, respectively.
The side effects of both techniques are quite moderate – with one important exception. While tES can induce only mild and temporary itching, tingling, and skin reddening when done properly, TMS might cause mild headaches, facial twitching, seizures in extreme cases.
For both TMS and tES, medical treatment must be performed mostly in clinical settings, which means you will have to find a clinician who provides these services in their clinic. However, one of the strengths of tES is the possibility to perform stimulation telemedically (under the remote guidance of a clinicians) via home-treatment. This is important as it will boost therapeutic effects for pathologies such as motor rehabilitation, depression, Alzheimer’s disease, etc in the comfort of one’s home. And it has been shown that the number of sessions modulates the length of the long-term plastic effects.
Interested in home-application of tCS? Check our home-kit here.
Polanía R, Nitsche M.A., Ruff C., Studying and modifying brain function with non-invasive brain stimulation, Nat. neurosci., 21:174–187 (2018)
Dayan E., Censor N., Buch E.R., Sandrini M, Cohen L.G., Noninvasive brain stimulation: from physiology to network dynamics and back, Nat. Neurosci., 16:838–844 (2013)
Salvador R., Wenger C., Miranda P.C. Investigating the cortical regions involved in MEP modulation in tDCS, Front. Cell. Neurosci. 9:405 (2015)
[NEWS] Brain stimulation improves depression symptoms, restores brain waves in clinical study — ScienceDaily
Date: March 11, 2019
Source: University of North Carolina Health Care
Summary: With a weak alternating electrical current sent through electrodes attached to the scalp, researchers successfully targeted a naturally occurring electrical pattern in a specific part of the brain and markedly improved depression symptoms in about 70 percent of participants in a clinical study.
With a weak alternating electrical current sent through electrodes attached to the scalp, UNC School of Medicine researchers successfully targeted a naturally occurring electrical pattern in a specific part of the brain and markedly improved depression symptoms in about 70 percent of participants in a clinical study.
The research, published in Translational Psychiatry, lays the groundwork for larger research studies to use a specific kind of electrical brain stimulation called transcranial alternating current stimulation (tACS) to treat people diagnosed with major depression.
“We conducted a small study of 32 people because this sort of approach had never been done before,” said senior author Flavio Frohlich, PhD, associate professor of psychiatry and director of the Carolina Center for Neurostimulation. “Now that we’ve documented how this kind of tACS can reduce depression symptoms, we can fine tune our approach to help many people in a relatively inexpensive, noninvasive way.”
Frohlich, who joined the UNC School of Medicine in 2011, is a leading pioneer in this field who also published the first clinical trials of tACS in schizophrenia and chronic pain.
His tACS approach is unlike the more common brain stimulation technique called transcranial direct stimulation (tDCS), which sends a steady stream of weak electricity through electrodes attached to various parts of the brain. That approach has had mixed results in treating various conditions, including depression. Frohlich’s tACS paradigm is newer and has not been investigated as thoroughly as tDCS. Frohlich’s approach focuses on each individual’s specific alpha oscillations, which appear as waves between 8 and 12 Hertz on an electroencephalogram (EEG). The waves in this range rise in predominance when we close our eyes and daydream, meditate, or conjure ideas — essentially when our brains shut out sensory stimuli, such as what we see, feel, and hear.
Previous research showed that people with depression featured imbalanced alpha oscillations; the waves were overactive in the left frontal cortex. Frohlich thought his team could target these oscillations to bring them back in synch with the alpha oscillations in the right frontal cortex. And if Frohlich’s team could achieve that, then maybe depression symptoms would be decreased.
His lab recruited 32 people diagnosed with depression and surveyed each participant before the study, according to the Montgomery-Åsberg Depression Rating Scale (MADRS), a standard measure of depression.
The participants were then separated into three groups. One group received the sham placebo stimulation — a brief electrical stimulus to mimic the sensation at the beginning of a tACS session. A control group received a 40-Hertz tACS intervention, well outside the range that the researchers thought would affect alpha oscillations. A third group received the treatment intervention — a 10-Hertz tACS electrical current that targeted each individual’s naturally occurring alpha waves. Each person underwent their invention for 40 minutes on five consecutive days. None of the participants knew which group they were in, and neither did the researchers, making this a randomized double-blinded clinical study — the gold standard in biomedical research. Each participant took the MADRS immediately following the five-day regimen, at two weeks, and again at four weeks.
Prior to the study, Frohlich set the primary outcome at four weeks, meaning that the main goal of the study was to assess whether tACS could bring each individual’s alpha waves back into balance and decrease symptoms of depression four weeks after the five-day intervention. He set this primary outcome because scientific literature on the study of tDCS also used the four-week mark.
Frohlich’s team found that participants in the 10-Hertz tACS group featured a decrease in alpha oscillations in the left frontal cortex; they were brought back in synch with the right side of the frontal cortex. But the researchers did not find a statistically significant decrease in depression symptoms in the 10-Hertz tACS group, as opposed to the sham or control groups at four weeks.
But when Frohlich’s team looked at data from two weeks after treatment, they found that 70 percent of people in the treatment group reported at least a 50 percent reduction of depression symptoms, according to their MADRS scores. This response rate was significantly higher than the one for the two other control groups. A few of the participants had such dramatic decreases that Frohlich’s team is currently writing case-studies on them. Participants in the placebo and control groups experienced no such reduction in symptoms.
“It’s important to note that this is a first-of-its kind study,” Frohlich said. “When we started this research with computer simulations and preclinical studies, it was unclear if we would see an effect in people days after tACS treatment — let alone if tACS could become a treatment for psychiatric illnesses. It was unclear what would happen if we treated people several days in a row or what effect we might see weeks later. So, the fact that we’ve seen such positive results from this study gives me confidence our approach could help many people with depression.”
Frohlich’s lab is currently recruiting for two similar follow-up studies.
Other authors of the Translational Psychiatry paper are co-first authors Morgan Alexander, study coordinator and graduate student, and Sankaraleengam Alagapan, PhD, a postdoctoral fellow, both in the department of psychiatry at UNC-Chapel Hill; David Rubinow, MD, the Assad Meymandi Distinguished Professor and Chair of Psychiatry at the UNC School of Medicine; former UNC postdoctoral fellow Caroline Lustenberger, PhD; and Courtney Lugo and Juliann Mellin, both study coordinators at the UNC School of Medicine.
This research was funded through grants from the Brain Behavior Research Foundation, National Institutes of Health, the BRAIN Initiative, and the Foundation of Hope.
Frohlich holds joint appointments at UNC-Chapel Hill in the department of cell biology and physiology and the Joint UNC-NC State Department of Biomedical Engineering. He is also a member of the UNC Neuroscience Center.
- Morgan L. Alexander, Sankaraleengam Alagapan, Courtney E. Lugo, Juliann M. Mellin, Caroline Lustenberger, David R. Rubinow, Flavio Fröhlich. Double-blind, randomized pilot clinical trial targeting alpha oscillations with transcranial alternating current stimulation (tACS) for the treatment of major depressive disorder (MDD). Translational Psychiatry, 2019; 9 (1) DOI: 10.1038/s41398-019-0439-0
[Abstract] Basic and functional effects of transcranial Electrical Stimulation (tES)—An introduction
[REVIEW] TRANSCRANIAL DIRECT CURRENT STIMULATION (tDCS) AND TRANSCRANIAL CURRENT ALTERNATING STIMULATION (tACS) REVIEW – Full Text PDF
This literature review is aimed to explore the main technical characteristics of both transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) using the latest research on both healthy and impaired subjects. These techniques have no oﬃcial standards developed yet. Our intent is to underline the main properties and problems linked with the application of those techniques which show diverse, and sometimes even opposite, results depending mainly on electrode positioning and underlying brain activity.
Among diﬀerent impairments that can aﬀect standard brain functions, we choose to focus primarily on stroke, because it is one of the most prevalent and severe disability worldwide . It is known that after a cerebrovascular accident, reorganization of neural tissues takes place . If the ischemic event occurs on the motor area and it is severe enough to block the spontaneous neural reorganization, it could lead to paresis or even paralysis of one or more body parts .
In order to ameliorate stroke rehabilitation, diﬀerent approaches have been carried out. Over the last decade, within the ﬁeld of functional rehabilitation, transcranial current stimulation (tCS) has garnered considerable attention. It is assumed to improve, above other, motor functions in both healthy and stroke individuals , , .
There are three diﬀerent types of tCS: transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS) and random noise stimulation (tRNS). All of them are non-invasive and involve low intensity current induction into the brain. Some studies have investi
gated the physiological basis of tDCS and tACS in order to get the picture of standard pattern that can be used for future research , .
This paper is oriented towards a broad audience who wants to understand the basic mechanisms of tDCS and tACS techniques. The main parameters of each type of stimulation and the implications related to its application on healthy subjects, stroke patients and individuals with unusual brain oscillations are discussed.
Low-intensity transcranial electrical stimulation (tES) methods are a group of noninvasive brain stimulation techniques, whereby currents are applied with intensities typically ranging between 1 and 2 mA, through the human scalp. These techniques have been shown to induce changes in cortical excitability and activity during and after the stimulation in a reversible manner. They include transcranial direct current simulation (tDCS), transcranial alternating current simulation (tACS), and transcranial random noise stimulation (tRNS).
Currently, an increasing number of studies have been published regarding the effects of tES on cognitive performance and behavior. Processes of learning and increases in cognitive performance are accompanied by changes in cortical plasticity. tES can impact upon these processes and is able to affect task execution. Many studies have been based on the accepted idea that by increasing cortical excitability (e.g., by applying anodal tDCS) or coherence of oscillatory activity (e.g., by applying tACS) an increase in performance should be detected; however, a number of studies now suggest that the basic knowledge of the mechanisms of action is insufficient to predict the outcome of applied stimulation on the execution of a cognitive or behavioral task, and so far no standard paradigms for increasing cortical plasticity changes during learning or cognitive tasks have been established.
The aim of this review is to summarize recent findings with regard to the effects of tES on behavior concentrating on the motor and visual areas…
Is transcranial current stimulation (tCS, including direct current, tDCS, alternating current, tACS, or random noise stimulation tRNS) effective for the treatment of depression?
Under what conditions? With what montages? We focus here on a review of the recent literature on this topic. We have relied on Google Scholar and also PubMed to carry out the search, including the terms of tDCS, tACS, tRNS as well as Depression (from March 2012 and till Sep 2013).
As you can read below, there quite a few encouraging results in this area, and study group sizes (the famous N) are moderately large. We try to indicate group size and the use of a sham-controlled, double-blind experimental technique. Most studies are careful about these crucial aspects. In addition, it is worth mentioning that there continues to be a lack of bad news from the safety point of view. This seems to be a common pattern of tDCS research (or tCS, in fact). I will discuss this further in a future post on an update on tCS Safety.
The typical target for treatment is anodal on the left DLPFC (F3 in the 10-20 EEG system) with the cathode over the contralateral orbit or, sometimes, over the right DLPFC. As in prior posts, in what follows we concentrate on relevant, study-oriented papers with patients, and leave reviews to the end. In order to make the reading lighter, we have edited the abstracts a bit (please click on the title link if you are interested in the paper)… Full Text PDF