2023-09-09 10:11:05
A patient in a waiting room.
Approved more than a decade ago, transcranial magnetic stimulation (TMS) is moderately effective. Tailoring treatment to individual brains can improve outcomes.
In the mid-1970s, a British researcher named Anthony Barker wanted to measure the speed at which electrical signals travel along long, thin nerves that can transmit signals from the brain to muscles like those in the hand, thereby triggering movement. To find out, he needed a way to stimulate people’s nerves.
Researchers had previously used electrodes placed on the skin to generate a magnetic field that penetrated human tissue, producing an electrical current that activated peripheral nerves in the limbs. But the technique was painful, burning the skin. Barker, of the University of Sheffield in England, and his colleagues began working on a better method.
In 1985, with promising results under their belt, they tried positioning the coil-shaped magnetic device they had developed on participants’ heads. The coil delivered rapidly alternating magnetic pulses to the region of the brain that controls movement, generating weak electrical currents in the brain tissue and activating neurons that control hand muscles. After regarding 20 milliseconds, the participants’ fingers twitched.
The technique, now called transcranial magnetic stimulation (TMS), has proven to be an essential tool for studying how the human brain functions. When targeted to specific regions of the brain, TMS can temporarily inhibit or enhance various functions – for example blocking the ability to speak, or making it easier to memorize a series of numbers. And when brain imaging technologies such as functional magnetic resonance imaging (fMRI) emerged in the 1990s, researchers might now “see” inside people’s brains when they received TMS stimulation . They were also able to observe how neural pathways respond differently to stimulation in psychiatric illnesses like schizophrenia and depression.
In recent decades, this basic research has given rise to new treatments that modify brain activity, with TMS therapies for depression at the forefront. In 2008, the U.S. Food and Drug Administration approved NeuroStar, the nation’s first TMS device for depression, and many other countries have since sanctioned the approach.
Yet even though TMS is now a widely available treatment for depression, many questions remain regarding this method. It’s not clear how long the benefits of TMS may last, for example, or why it seems to work for some people with depression but not others. Another challenge is disentangling the effects of TMS from the placebo effect – when a person believes they will benefit from the treatment and that their condition will improve even if they receive a form of “sham” stimulation.
Whether TMS can “cure” depression “is an open question – there is evidence for and once morest,” says David Pitcher, a cognitive neuroscientist at the University of York who wrote a 2021 overview in the Annual Review of Psychology on the use of TMS to study human cognition. . But as researchers refine their approach and conduct more sophisticated clinical trials, TMS is emerging as a powerful tool for dissecting the complexities of depression — and for some people, for releasing its grip.
From electric fish to magnets
TMS may be relatively new, but the use of electricity as medicine is ancient. As early as the 1st century CE, Roman doctors recommended using live electric torpedo fish to treat headaches. Nearly two millennia later, in the 1930s, doctors discovered that inducing brain seizures with electricity might reduce the symptoms of schizophrenia and other forms of mental illness.
This was the beginning of electroconvulsive therapy (ECT), pejoratively known as shock therapy. The practice spread quickly despite the risk of memory loss, confusion and injuries from muscle spasms. Administering ECT without fully informing patients regarding the therapy and its risks also raised ethical concerns, a problem that medicine as a whole was seriously facing at the time.
Eventually, muscle relaxants, anesthetics, and stricter consent protocols improved ECT, although side effects such as headaches and temporary loss of short-term memory are still reported. ECT remains one of the most effective treatments for people who do not respond to first-line antidepressant treatments such as serotonin reuptake inhibitors (SSRIs), a group of medications that includes Zoloft and Prozac .
Yet these medications and ECT are difficult to control precisely because they affect the entire brain. A more targeted approach is deep brain stimulation (DBS), which involves directly stimulating neurons with surgically implanted electrodes in regions known to affect mood and motivation. DBS has shown promise in pilot studies and has been approved for investigational use in 2022, but has not yet received clinical approval.
In contrast, TMS requires no surgery and has fewer side effects than ECT, says Alvaro Pascual-Leone, a neurologist at Harvard Medical School. Although it is not as easy to target a specific region of the brain as DBS, it is much more precise than antidepressants or ECT.
Pascual-Leone began studying magnetic stimulation to treat major depressive disorder in the early 1990s. This excited him because of the ability to focus stimulation non-invasively and its few and relatively minor side effects. , which usually include scalp discomfort, tingling, spasms and dizziness and, rarely, seizures and hearing loss.
Although its mechanisms are not fully understood, TMS appears to work by reconfiguring neural circuits, thereby starting more typical communication between different areas of the brain, says Noah S. Philip, a psychiatrist at Brown University who studies TMS to treat the Depression.
At rest, people with depression often have reduced activity levels in an area of the brain called the dorsolateral prefrontal cortex (DLPFC) compared to non-depressed people, neuroimaging studies have shown. The region is a prime site for TMS therapy, says Philip. Center for short-term memory, planning and abstract reasoning, the DLPFC is connected to several brain circuits involved in depression: the salience network, which allows us to focus attention on certain things and ignore others ; the default mode network, which is active when a person is not engaged in any particular task; and the executive network, key to planning, decision-making and impulse control. Together, these circuits underlie our ability to focus on relevant information and shift our attention between autonomous thought and our environment.
Scientists believe that abnormal communication between networks can lead to constant ruminations, self-criticism and a tendency to focus too much on the negative aspects of life that people with depression often experience. Using fMRI to measure how network nodes communicate before and following TMS, Philip, among other researchers, found that multiple sessions of TMS can restore more typical activity. He says the change can last more than a year and can possibly be maintained longer with additional TMS treatments.
The long-lasting effects of TMS are likely due to remodeling of neuronal connections caused by microscopic changes in brain cells, Philip explains. Studies have shown that TMS can stimulate neurons to sprout new dendrites, the branching appendages that receive signals from other neurons.
An early clinical trial found that people with severe depression who received TMS daily for several weeks were up to four times more likely to go into remission than participants in control groups, who were fitted with a TMS device but had not received any real stimulation. In later studies that lacked control groups (i.e., patients and doctors knew that TMS was being administered), 30% to 40% of patients who did not improve on medication went into remission. , defined by a low score on a standard measure such as the Hamilton Depression Rating Scale. That’s regarding equal to the number of people who respond well to antidepressant medications, according to a 2013 study published in Current Opinion in Psychiatry.
However, many questions remain, including whether better results can be achieved by targeting specific regions in individual patients. “Some people with depression experience sadness, others suffer more from a lack of motivation or apathy,” explains Pascual-Leone. “Some people eat too much; others eat too little. Unlike more general treatments, he says, TMS has such targeting potential.
Tailor-made brain stimulation
In many clinics and research laboratories, the process of determining where to place TMS coils on a person’s head is relatively simple. The FDA-approved method is reminiscent of Barker’s original experiments: A participant sticks out their thumb like a hitchhiker, and technicians move the magnetic coil around their scalp until electrical stimulation hits part of the motor cortex which makes his thumb twitch involuntarily. Using this location as a cue, technicians then move the coil to a position that targets the left DLPFC.
The approach is moderately effective, but many researchers believe it does not sufficiently account for the wide variations in brain structure from one individual to another. Increasingly, scientists are using fMRI and other brain imaging technologies to tailor TMS stimulation to each person’s unique brain structure and observe how it affects their neural activity patterns. “An exciting advancement over the last 10 years with TMS is using it on patients and then neuroimaging their brains to look at changes in connectivity between the DLPFC and areas we know it’s connected to “, says Pitcher from the University of York.
A team of researchers at Stanford University, led by psychiatrist Nolan Williams, director of the Stanford Brain Stimulation Lab, is one of the groups developing this combined approach. In a small 2021 study, the team used fMRI scans, which measure changes in blood flow associated with brain activity, to localize a small subregion of the DLPFC in individual patients. The activity of this subregion presents an inverse relationship with that of another area of the brain, the subgenual cingulate (SGC): in people suffering from depression, the activity of the SGC is reinforced while the activity of the DLPFC subregion is reduced. Conversely, the more active the DLPFC node, the less active the SGC becomes. The SGC, for its part, appears to influence the default mode network, anchoring people in negative patterns of self-rumination.
In the Stanford study, Williams and colleagues targeted the DLPFC subregion in 29 people with what’s called treatment-resistant depression: They scored “moderate to severe” on an assessment. standard that takes into account how they responded to previous treatments for depression as well as the duration and severity of the depression. their symptoms. The group received an accelerated experimental treatment regimen with more than one daily TMS session. To control for a possible placebo effect, some group members were randomly assigned to receive sham stimulation that resembled TMS but did not deliver electromagnetic pulses.
After five days of treatment, 79 percent of participants who received the targeted TMS experienced remission, compared to 13 percent of the control group. The team also observed that stimulating the area of the DLPFC most strongly connected to the SGC normalizes the relevant connections between the three regions. “You see it when you scan people followingwards,” Williams says.
One participant in his early 60s, Tommy Van Brocklin, had struggled with depression for regarding 45 years. In recent years, the medications he was taking stopped working.
The five-day treatment left him feeling “like a tree being pecked by a woodpecker” because of the knocking noises made by the TMS machine, he jokes. But on the third day, he noticed a difference in his mood: “Everything seemed to click, and it felt good. »
Researchers believe this individualized approach to TMS treatment might provide a rapid and effective intervention for suicidal patients. In 2022, Williams’ method cleared a major regulatory hurdle: the FDA granted approval for it to be marketed.
Seeing such high remission rates following just five days of treatment — a very practical intervention — is exciting, says William T. Regenold, director of a research unit that studies noninvasive neuromodulation at the U.S. National Institutes of Health mental. He and his colleagues are currently conducting a clinical trial studying changes in brain activity in severely depressed patients who receive TMS in combination with talk therapy. “The idea is to have a synergistic effect between psychotherapy and TMS,” he explains.
By tailoring the treatment to each person’s brain anatomy, the Stanford study’s success is “very consistent with notions of precision medicine – individually targeted interventions,” says Pascual-Leone.
But there is still a lot of work to be done. An urgent challenge is to extract the benefits of stimulating the placebo effect; some research suggests that this effect plays a role in the improvements many experience from TMS. This problem is not unique to brain stimulation, but it is common to all treatments for depression. Several meta-analyses of the placebo effect of antidepressants, for example, have found that people who take inactive pills experience a 20 to 40 percent improvement in their symptoms, typically measured by one of several standard questionnaires.
Research groups are starting to get clearer and more impressive results by using brain scans to guide individualized stimulation, as the Stanford team did. But more studies are needed to determine whether TMS will have similar success in broader populations, as well as in groups such as adolescents, older adults and people with conditions that often accompany depression, such as depression. anxiety and post-traumatic stress. Some labs are experimenting with designing TMS devices – for example comparing figure-8 magnetic coils to those shaped like butterfly wings – and changing the stimulation frequency to see how this changes brain activity and treatment outcomes .
Yet many fundamental questions regarding TMS remain. Although scientists know that it disrupts normal neuronal firing, “we don’t really understand how TMS works mechanistically” to change brain states like mood, Pitcher says. One reason is that researchers can’t record the activity of a single neuron in a human and do TMS at the same time, he explains. It is not clear why certain TMS frequencies appear to increase activity in some regions of the brain, while decreasing it in other areas – nor how the new neuronal connections stimulated by TMS affect different brain networks.
“Luckily, we can do this work, advancing science while helping people with debilitating illnesses,” says Pascual-Leone. “It’s an incredible position to be in.” »
Translated and published with kind permission of Knowable Magazine. The original article is to be found HERE.
1694256770
#Fight #depression #magnetic #therapy #gained #effectiveness
