Tag: tDCS

11/15/22

Brain Stimulation or Brain Damage? Part 1

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Nexstim won FDA clearance for its noninvasive brain stimulation system to treat major depression in November 2017. The Nexstim CEO, Martin Jamieson, said the clearance was a critical milestone for the commercialization of their transcranial magnetic stimulation (TMS) device in the U.S. Then in February of 2019 the FDA cleared a drastically reduced 3-minute session protocol to treat major depression with Nexstim’s NBT (Navigated Brain Therapy) System. The previous protocol time was 37 minutes. The Theta Burst Stimulation is a newer form of repetitive TMS that allows for stimulation to specific areas of the patient’s brain. “The company believes that the shorter protocol will increase ease of use for the NBT system.”

The new 3-minute NBT protocol was approved based on results from a study of 414 patients with treatment-resistant depression, which found that intermittent Theta Burst Stimulation was non-inferior to high-frequency transcranial magnetic stimulation.

There is also Humm, a transcranial alternating current stimulation (tACS) device that claims it can improve your cognitive function and memory. “Humm is a wearable patch that gently stimulates the brain’s natural rhythms to strengthen memory.” Neuroskeptic said he was pleasantly surprised with Humm’s reported study, which he said actually looked solid. Although the study was not published, he thought it would pass peer-review. He noted while there is evidence that individually-tailored theta tACS can benefit working memory, other studies show a disruption of working memory. “My point is that, a priori, there is no reason to assume a beneficial effect of this kind of stimulation.”

And most recently, the British government approved Flow, a headset claimed to reduce chronic depression symptoms. The website for Flow Neuroscience claims most users notice a reduction of their symptoms after 3-4 weeks. The device sends a small jolt of electricity through the skull into the prefrontal cortex. Users are instructed to wear the headset for a half-hour every three days over the course of six weeks. Additionally, they are encouraged to use an app, which provides useful tips such as reminders to get enough sleep, eat right and exercise.

The technology, known as transcranial direct current stimulation [tDCS], has been the subject of numerous tests, most of which have found that it provides some degree of relief from depression symptoms. Many have concluded that it is at least as effective as antidepressants, but without the side effects. Thus far, none of the trials have found any adverse effects of such treatment other than reddened skin where the electrodes are placed and the occasional headache. Such treatments have been found to change the potential of neurons—in some cases, making them fire more often, and in others less often. People with chronic depression typically experience less neural activity in the left side of their prefrontal cortex—the mild shocks are meant to increase such activity to match that in the right side. Some of the trial results have even shown that in some cases, mild electrical stimulation can encourage the growth of new neural connections, perhaps reducing depression symptoms permanently.

A study by Clarke et al. reported in the June 2019 issue of the Journal of Affective Disorders investigated the efficacy of repetitive transcranial magnetic stimulation (rTMS) in patients with treatment resistant depression and comorbid anxiety. Their study included 248 patients with treatment resistant depression. Of these, 172 also had one or more comorbid anxiety disorders. The researchers found that rTMS therapy showed improvement in depression in patients with major depression alone and those with comorbid anxiety. 39.5% of patients with comorbid anxiety disorders met the response criteria defined in the study and 23.3% met the criteria for remission.

Psychiatry Advisor reported the researchers said: “This study showed that rTMS is equally effective for treating depression, regardless of whether there are comorbid anxiety disorders or not. . . [There] is a role for future research into TMS as a treatment for patients with anxiety conditions without major depression.” TMS or rTMS devices are used typically for treatment-resistant depression and can only penetrate a few centimeters into the outer cortex of the brain. The strength of these devices declines rapidly the farther away the machine is positioned from the scalp. See “Better Living Through Brain Stimulation” for more information on rTMS and TMS.

If you want to target deeper regions of the brain, a more direct stimulation method like tDCS or tACS is needed. tDCS devices are inexpensive and easy to use. They are promoted like patent medicines, able to benefit problems such as: migraine, chronic pain, post-stroke paralysis, Parkinson’s disease, depression, tinnitus, fibromyalgia, marijuana craving and the tendency to lie; and they do not require a prescription. tACS is supposed to reverse the decline of working memory related to the aging brain. See “Jump Starting Your Brain” and “Electrical Psychiatry” for more information on tDCS and tACS.

With deep brain stimulation (DBS), we move to a procedure that requires surgery to implant electrodes into a patient’s brain. Wires connect the electrodes to a device implanted underneath the person’s skin. DBS devices are considered to be a last resort treatment method for conditions like Parkinson’s disease and Tourette Syndrome, and they carry risks of adverse side effects such as mood, behavior and personality changes. These can include suicide, depression, mania and serious impulse control issues, such as hypomania, addiction (gambling, shopping, drugs, alcohol) and hypersexuality. See “Deep Brain Jolts” for more information on DBS. See “Deep Brain Problems” for more information on the adverse effects of DBS.

An odd, unanticipated adverse effect has emerged with DBS. According to The New York Times, DBS electronic implants reduced Parkinson’s symptoms, but they also expunged some patients’ proficiency for swimming. “A lifelong swimmer leapt into deep water near his lakeside home and was horrified to find himself completely unable to swim. Had his wife not rescued him, he might have drowned.” Somehow the signals from the DBS device had deleted his ability to coordinate his arms and legs for swimming.

An article in the journal Neurology by a medical team from the University of Zurich documented nine cases among 250 patients. One of the coauthors said he thought the swimming issue was in a minority of patients, because some are still able to swim and they don’t know why. “We have no clue. They are treated in the same region of the brain. But this is life-threatening, and we need to pay more attention in the future.” In 2015 Australian doctors reported one patient who could not even float with the device turned on. With the device off, he could swim laps. Three other patients with DBS stimulators for Parkinson’s have drowned, but “they did not if the deaths were related to the device.”

Now DBS is targeting addiction treatment and China is emerging as the center for this research. AP News noted how scientists in Europe have struggled to recruit patients for their DBS addiction studies (No surprise, given the above brief description of DBS). In the U.S. there are ethical, social and scientific questions (in addition to the cost of around $100,000 to implant), as well as the adverse effects from surgery. China’s anti-drug laws can force people into years of compulsory treatment, including “rehabilitation” through labor. According to ClinicalTrails.gov, there are now 12 registered DBS clinical trials for addiction being conducted globally, 8 are in China; one each in France, Israel, Canada, and Germany. The trials are primarily for opiate/opioid use and misuse, but there are some for methamphetamine, cocaine, alcohol, and morbid obesity. Some critics believe this surgery should not be permitted.

They argue that such human experiments are premature, and will not address the complex biological, social and psychological factors that drive addiction. Scientists don’t fully understand how DBS works and there is still debate about where electrodes should be placed to treat addiction. There is also skepticism in the global scientific community about the general quality and ethical rigor — particularly around issues like informed consent — of clinical trials done in China.

Dr. Nader Pouratain, a neurosurgeon at UCLA, is investigating the use of DBS for chronic pain. He thought it was time to research DBS for drug addiction. However, only “if we can move forward in ethical, well-informed, well-designed studies.” At least two U.S. laboratories dropped clinical trials of DBS treatment for alcoholism over concerns the study design and preliminary results did not seem to justify the risks. Dr. Emad Eskandar, the chairman of neurological surgery at Albert Einstein College of Medicine said: “The lack of scientific clarity, the important but strict regulatory regime, along with the high cost and risk of surgery make clinical trials of DBS for addiction in the U.S. difficult at the present time.” The FDA blocked an application for a Chinese DBS device for a multi-site, opioid addiction.

In February of 2019, the FDA approved a small, separate trial of DBS for opioid use disorder at the West Virginia University Rockefeller Neuroscience Institute. On November 5, 2019 the Rockefeller Neuroscience Institute announced the launch of the first-in-the-U.S. clinical trial of DBS for treatment-resistant opioid use disorder. The first participant is a 33-year-old man with excessive opioid and benzodiazepine use for more than a decade. The first phase will include 3 additional participants.

ScienceAlert (the article was originally published by The Washington Post) reported Dr. Rezai said he wasn’t advocating DBS as a first line or even a second line treatment. “It’s for people who have failed everything, because it is brain surgery.” He acknowledged that doctors and researchers do not fully understand how this (DBS) works. “The exact mechanisms are not known.” By modulating the reward circuit, which relies on dopamine, “you’re getting better control, so you’re not craving dopamine as much.”

The trial is partly funded by the National Institute on Drug Abuse (NIDA). The director of NIDA, Nora Volkow, said she has spoken with a few of the patients who underwent the procedure in China and thought the surgery had promise. She thought the surgery had disrupted the brain’s fixation on opioids. “They reported more of an ability to engage, to feel interest in other things.” She suggested that brain’s fixation on opioids may be disrupted by the surgery. Helen Mayberg, the director of the Center of Advanced Circuit Therapeutics at the Mt. Sinai Medical Center School of Medicine, said the logic of the effort was sound and the circuitry of the targeted area of the brain was well-mapped compared to other regions. “The key question is whether the researchers have found the precise spot for insertion of the electrodes.”

Brain stimulation (magnetic or electric) has been progressively moving from the laboratory to the clinic and even into the privacy of your home. It seems to me that as brain stimulation devices enter the market place, they are being promoted like patent medicines were a hundred or more years ago. Most of the devices are noninvasive, except for DBS devices, which require brain surgery. DBS has been approved and used to treat medical issues such as chronic pain, Parkinson’s and Tourette Syndrome. And now doctors and researchers are trying it with another desperate and vulnerable population—addicts.

There is a growing global opioid crisis and DBS is being researched and promoted as an addiction treatment for individuals who have failed other approaches. But is DBS treatment worth the risk with addiction? DBS supporters like those mentioned here would say yes. The 2019 World Drug Report estimated there were 35 million worldwide who suffer from drug use disorders. More specifically, there were more than 47,000 opioid overdose deaths in the U.S. in 2017, an increase of 13% from the previous year. The number of new psychoactive substances (NPS) that are synthetic opioids rose from 1 substance in 2009 to 15 in 2015 and 46 in 2017, accounting for 29% of the newly identified NPS in 2017.

Currently there are an estimated 180,000 people globally who have DBS devices implanted in their brains. But that would increase exponentially if DBS becomes a more widespread treatment for addiction. Yet Ali Rezai, the executive chairman of the West Virginia Rockefeller Neuroscience Center (where the FDA clinical trial is being conducted) acknowledged they do not fully understand how DBS works. There are serious ethical, social and scientific questions about DBS as well as a variety of adverse effects that result from the surgery. We will examine some of these in part 2.

Originally posted on January 28, 2020.

06/18/19

Better Living Through Brain Stimulation

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Electrical stimulation to treat medical conditions is not the new, cutting edge research and treatment one would expect. Besides electroconvulsive therapy (ECT), which originated in the 1930s, there is evidence the ancient Egyptians knew about the electrical properties of Nile catfish. However, it’s not clear if they used them for medical purposes. The first evidence for electrical “treatment” dates from Plato and Aristotle who described the ability of the torpedo fish to generate so-called “curative effects.” Scribonius Largus (1-50 AD) and Galen (130-201 AD) said the torpedo fish could be used to treat headache, gout, and epilepsy.

Today, not only is there ECT, but Transcranial Magnetic Stimulation (TMS), Repetitive Transcranial Magnetic Stimulation (rTMS), Transcranial Direct Current Stimulation (tDCS), Deep Brain Stimulation (DBS) and more. There are two, perhaps three needed distinctions. First, every type of brain stimulation except DBS is noninvasive—meaning they do not require surgery. DBS surgically implants parts of the stimulation device into the patient’s brain. The second distinction is that tDCS is the only brain stimulation that does not require a physician’s prescription. It is also more affordable and “safer.”

Thirdly, ECT uses very high current levels, around 800 milliamps, to induce an intentional, controlled seizure. For a comparison, tDCS uses a maximum of 2 milliamps. “Due to the severity of the effects produced by Electroconvulsive Therapy, the patient is almost always sedated during stimulation, which lasts for an average of 1 to 6 seconds. The required use of sedation greatly increases the potential, and severity of any negative side effects.” Sedation during ECT is to prevent fractures from severe muscle spasms, according to Peter Breggin in Brain Disabling Treatment in Psychiatry, (p. 242):

For the past 40 and more years, a modified form of ECT had been standard, involving sedation with a short-acting barbiturate, muscle paralysis with a curare derivative or similar drugs that prevent activation of the muscles of the body and artificial respiration with oxygen. The purpose of these modifications was not, as some advocates claim, to reduce memory loss and brain damage. Muscle paralysis was intended to prevent fractures from severe muscle spasms, while the artificial respiration kept the paralyzed patient breathing.

TMS and rTMS are electromagnetic therapies typically used for treatment-resistant depression. Patients sit in a specially designed chair with positioning frames used to hold their head in place during treatment. “Positioning frames are required for TMS therapy because the stimulation apparatus does not touch the individual’s head, but instead hovers just a few centimeters above the scalp.” The key difference with rTMS is the repetitive nature of the magnetic pulses, which is rapidly increased, switching between positive and negative polarities in milliseconds. The increased strength of electromagnetic induction in rTMS may potentially “solidify longer lasting changes in the brain, whereby TMS may only induce short-term changes.” Yet a recent study found no difference in remission rates between rTMS and sham rTMS.

TMS devices can only penetrate a few centimeters into the outer cortex of the brain. Because of the way electromagnetic fields operate, the strength of TMS devices declines rapidly the farther away the machine is positioned from the scalp. So, if targeting deeper regions of the brain is what you want, a more direct stimulation method like tDCS is needed. tDCS devices are available for home use. However, because of the complex nature of the technology and the need for precise positioning of the electrodes, it is recommended they only be used within clinical settings. Another consideration is that you are sending an electric current, albeit a low one, to modulate neuronal excitability in a specific area of your brain.

An article in Psychological Medicine gave a brief history of tDCS, and noted the 20th century discovery in Iraq of the “Baghdad battery,” a DC generator dated from the ancient Persian civilization (490 BC). It was possibly used for medical purposes. It wasn’t until the 1800s that a DC battery was invented by Luigi Galvani. His nephew, Giovanni Aldini, was the first person to use DC for clinical purposes. A 27-year old farmer was treated for melancholy madness (major depression). “The patient’s mood progressively improved so that Lazarini [the patient] was apparently completely cured several weeks after the beginning of the treatment.”

It wasn’t until 1998 that modern tDCS was developed. Technological innovation has enabled electronic and biomedical engineers to build “precise tDCS devices with better control of stimulation parameters” than older devices—and do so at reduced costs. This led some people to experiment with self-administering tDCS and sometimes having tDCS touted as a ‘miracle device.’ However, even the receptive authors of the article on tDCS cautioned against such media attention. They urged careful, neutral presentation of data to the public. “Sensationalistic news about the benefits of tDCS leads people to self-administer stimulation, as we can see in some Internet do-it-yourself tDCS forums.”

tDCS devices are inexpensive and easy to use. There are even YouTube videos of individuals experimenting on themselves. Dan Hurley published an article for The New York Times, describing the history and science of tDCS as well as his personal experience with it. He described the work of Dr. Felipe Fregni, an Associate Professor at Harvard. He has written extensively about the potential benefits of tDCS, including its effects on “migraine, chronic pain, post-stroke paralysis, Parkinson’s disease, depression, tinnitus, fibromyalgia, marijuana craving and, strangely enough, the tendency to lie.” Dr. Fregni said the main safety concern is that individuals have begun treat themselves: “What they fail to realize is that applying too much current, for too long, or to the wrong spot on the skull, could be extremely dangerous.” See “Jump Starting Your Brain” for more information and concerns with tDCS.

While not technically tDCS, the FDA recently approved a new cranial electrotherapy stimulator (CES) for the treatment of anxiety, depression and insomnia. The Cervella Cranial Electrotherapy Stimulator uses a Bluetooth-enabled set of headphones and an app to deliver a low-level, constant current to the individual’s cranium. According to the parent company, Cervella allows for automated recoding of treatment data, reminders and analytics aimed at improving patient outcomes. You also need a prescription in order to purchase one for the cost of $695.

Another form of electrostimulation called transcranial alternating-current stimulation (tACS) recently demonstrated the possibility of reversing the decline of working memory that comes with the aging brain. After 25 minutes of stimulation, the researchers found a rapid improvement in working memory for adults aged 60 to 76 years-old. The effects outlasted a 50-minute post-stimulation period. “The results provide insight into the physiological foundations of age-related cognitive impairment and contribute to groundwork for future non-pharmacological interventions targeting aspects of cognitive decline.”

Working memory is responsible for decision-making and allowing us to retain and access information such as names, phone numbers, and where we’ve put things. Age and cognitive deterioration in disorders like dementia contribute to the decline of working memory. The hypothesis tested by this study is that working memory operates by slow, low-frequency theta rhythms synchronizing with faster, gamma rhythms between the prefrontal and temporal areas in the brain. When these two areas are on the same wave length, “communication is tight, and working memory functions seamlessly.” As we age, these brain areas lose their synchronicity.

Interestingly, when a targeted form of tACS stimulation (HD-tACS) was used on participants, the age-related synchronization discrepancies disappeared. “HD-tACS appeared to eliminate age-related impairment in working-memory accuracy.”  In a related test, young adults with poor working memory received the HD-tACS stimulation and also improved their results. “We could boost their working memory even though they weren’t in their 60s or 70s.”

Neuroscientists, including the lead author of the study, cautioned that more work needed to be done with HD-tACS. The boost in performance may be statistically significant, but not clinically significant. This is also only one study so far. “I’d like to see this replicated by other labs, and extended to test other aspects of working memory.” STAT News said for HD-tACS stimulation to become a treatment for working memory deficits, “it would have to overcome a long list of hurdles, starting with proof that it’s safe.” Regardless of whether this experiment results in practical applications, it does provide evidence of the differences in working memory with older adults: “Brain circuits become functionally disconnected and fall out of synchrony.”

Deep Brain Stimulation (DBS) is an entirely different animal. A preliminary surgical procedure implants part of the device into a patient’s brain. Wires connecting the electrodes to the device, and sometimes the device itself, are implanted underneath the skin’s surface. DBS is a relatively new technique and considered to be a last resort treatment method, as are TMS and ECT. There are immense risks to DBS and currently it is only used to treat severe neurological conditions like Essential Tremor, Parkinson’s Disease, Tourettes Syndrome, and Dystonia. Long-term studies of Parkinson’s patients treated with DBS have shown they have DBS-related scar tissue in their brains. There have also been serious mood, behavior and personality changes documented.

These include suicide, depression, apathy, fatigue, mania and serious impulse control issues, such as hypomania, aggression, addiction (to gambling, shopping, drugs, alcohol) and hypersexuality, sometimes resulting in criminal behaviour, including pedophilia.

And by the way, they aren’t quite sure how it works. See, “Deep Brain Jolts” and “Deep Brain Problems” for more information on DBS.

None of the above-described methods of brain stimulation should be used at home without a prescription or the supervision of a doctor, including tDCS and tACS. There are potential serious adverse effects for some procedures like ECT and DBS. Better memory and living through brain stimulation is still a future hope and may just be a pipe dream. For more on issues with electrical brain stimulation, also see “Electrical Psychiatry.”

05/20/15

Jump Starting Your Brain

© : Birgit Reitz-Hofmann | 123RF.com
© : Birgit Reitz-Hofmann | 123RF.com

Of course, there is research into using low dose electrical stimulation of the brain, a technique called transcranial direct current stimulation (tDCS). Dan Hurley published an article in the online magazine for The New York Times, Jumper Cables for the Mind, where he described the science and history of tDCS as well as his personal experience with it. It uses less than 1 percent of the electricity necessary for electroconvulsive therapy and can be powered by an ordinary nine-volt battery. Papers published in peer-reviewed scientific journals have claimed tDCS can improve:

Everything from working memory to long-term memory, math calculations, reading ability, solving difficult problems, piano playing, complex verbal thought, planning, visual memory, the ability to categorize, the capacity for insight, post-stroke paralysis and aphasia, chronic pain and even depression. Effects have been shown to last for weeks or months.

Felipe Fregni, the physician and neurophysiologist where Hurley received tDCS, said that it won’t make you superhuman, “but it may allow you to work at your maximum capacity.” He said the strongest evidence for its effectiveness was for depression. By itself, he said tDCS was as effective as Zoloft at relieving depression. “But when you combine the two, you have a synergistic effect, larger than either alone. That’s how I see the effects of tDCS, enhancing something else.” Looking at the JAMA Psychiatry abstract for Fregni’s published article, the researchers also found that out of 125 participants in the study, there were 7 cases of treatment-emergent mania or hypomania—5 of which were in the combined treatment group. So one the things enhanced by combining the use of Zoloft and tDCS was mania and hypomania.

Hypomania is a mood state that is less intense than mania. The individual is impulsive, shows a lack of restraint in social situations and is a poor judge of risky activities. Motor, emotional and cognitive abilities could be effected. The person may be euphoric or irritable, but typically to a lesser intensity than in mania. Their characteristic behaviors are being very energetic and talkative. They are quite confident while verbalizing a flight of creative ideas.

Because of the inexpensiveness and easy application of tDCS, people are treating themselves with kits and homemade devices. Hurley indicated that YouTube videos showing individuals experimenting on their own brains are available. They look more foolhardy than the cast of “Jackass,” he said.  “What they fail to realize is that applying too much current, for too long, or to the wrong spot on the skull, could be extremely dangerous.” Here seems to be one example of what he meant: “Still Zapping My Brain.” Yet there is a good bit of serious research a well: tDCS for Cogntive Enhancement or Centre for Brain Science: Transcranial Direct Current Stimulation (tDCS).

So-called DIY head zappers ignore the caution from scientists that tDCS is not ready for home use. The research is preliminary and stimulation could be dangerous. Home use is only as good as the person who built and operated the system. Some people have posted online images of scalp burns from improper current.  There have been some rare reports of manic episodes and even temporary paralysis.

“We are in such a fog of ignorance,” says neuroethicist Hank Greely of Stanford Law School, who studies how brain research intersects with society. “We really need to know more about how this works.”

Caroline Williams at NewScientist.com reported that Jared Horvath and others at the University of Melbourne reviewed more than 100 studies of tDCS and only found one that was convincing. He said there didn’t seem to be any significant or reliable effect of tDCS on blood flow, electrical, or evoked activity within the brain. tDCS supporters dispute the findings. Horvath and his research team are finalizing another analysis that looks at the evidence for cognitive and behavioral change after tDCS. Vincent Walsh, a cognitive neuroscientist at University College London is not convinced there will be any supportive results.

In terms of cognition, which is the other aspect that people make claims about, tDCS is massively hyped. The danger is that people have been promised better memories, better reading, better maths, increased intelligence… you name it. The effects are small, short lasting, and no substantial claims have been replicated across laboratories. This paper [Horvath’s] is hopefully the beginning of a counterweight to all the bullshit.

Horvath has recently published his further research into the efficacy of tDCS, claiming he found no evidence of cognitive effects from a single-session of tDCS. What was unique about this study is that Horvath and his colleagues only included independently replicated studies. This means an originally published study that another research group had repeated. “Our quantitative review does not support the idea that tDCS generates a reliable effect on cognition in healthy adults.” Of the 59 analyses conducted, no significant effect for tDCS was found—regardless of the inclusion laxity of the studies.

Neuroskeptic, a British neuroscientist, pointed out the exclusion of non-replicated studies was an unusual restriction. However, it seems to me that the intent was to correct for the research problems with publication bias (see “Open Access Could ‘KO’ Publication Bias”). He quoted Nick Davis, who has published several papers about tDCS, who said Horvath’s review was useful, helping researchers think about the way they talk about the effects of tDCS. Davis remains optimistic about the future of tDCS.

tDCS is still a developing technology. I think that with more principled methods of targeting the current flow to the desired brain area, we will see tDCS become one of the standard tools of cognitive neuroscience, just as EEG and fMRI have become.