Magnetic pulses applied non-invasively to the scalp can stimulate the brain, to reverse brain changes, and to bring about rapid relief to severely depressed patients for whom standard treatments may have failed. This non-invasive brain stimulation modality is called repetitive transcranial magnetic stimulation (rTMS).
rTMS is based on the phenomenon of electromagnetic mutual induction, first reported by Michael Faraday in 1831. In 1985, Anthony Barker and his colleagues developed the first modern TMS device. rTMS generates brief electromagnetic pulses via an insulated coil placed over the scalp. These magnetic pulses non-invasively modulate the cortical activity of the brain.
On May 15, a study by Stanford University researchers reported some evidence that in people without depression, a part of the brain called the anterior insula sends signals to another part called the anterior cingulate cortex, whereas in people with depression, the signal goes the other way. According to the researchers, TMS may be alleviating depression by reversing the signal to go the right way.
Daily rTMS stimulation for several weeks has also been shown to be effective in reducing the symptoms of a range of neuropsychiatric disorders.
In 2008, the U.S. Food and Drug Administration (FDA) approved TMS as a treatment for clinical depression.
The use of TMS is based on the following principle: if a conducting medium, such as the brain, is adjacent to a magnetic field, a current will be induced in the conducting medium. In TMS, an electromagnetic coil is placed on the scalp. Passing intense electrical pulses in the coil produces a powerful magnetic field – typically about 2 tesla – which results in current flow in brain tissue and the depolarisation of brain cells.
The neuropsychological effects of TMS are particularly likely when a current is delivered in repetitive trains rather than as single pulses. If the stimulation occurs more quickly than once per second (1 Hz), it is called fast rTMS. The use of appropriately shaped coils allows reasonably localised stimulation of specific brain areas.
The person receiving rTMS sits in a comfortable chair, is awake and alert during the treatment session. It’s quite different from electroconvulsive therapy (ECT). Unlike ECT, rTMS does not involve producing a seizure, and does not require the person to be asleep or under anaesthetic.
Why does TMS work?
rTMS stimulation, over the course of a few weeks, increases neuronal activity in the area under the coil. It also changes the strength of connections between different areas of the brain. There is some reason to believe this restores the normal interaction between brain regions, although such hypotheses require further testing and replication.
By briefly passing a current through a coil of wires, a strong and rapidly fluctuating magnetic field can be formed. This generates electrical currents in the underlying brain tissue. This also affects the membrane potential of nearby brain cells.
rTMS can stimulate specific brain regions, such as the sensory or motor areas, to evoke corresponding sensory or motor responses. It can also interfere with ongoing brain activity and act as a brief virtual lesion.
Antidepressant medications may act in similar ways, but less directly. The chemicals they affect can influence brain function quite widely, turning activity or connectivity in brain circuits up or down. rTMS likely does this more directly. By directly making nerve cells fire, rTMS can directly change their activity levels. These more direct actions could possibly explain why rTMS may work in some people who have not responded to medication.
Clinical trials have found that rTMS treatments result in a gradual improvement in depression. A person’s mood will slowly lift, usually over the course of several weeks; they will become more interested in things, sleep better, be more motivated, and have more energy.
In people who respond, depression can go away for several months up to many years. If depression returns, most people will get better again with further treatment.
What are the clinical applications?
TMS has been used for many years in clinical neurophysiology to explore the integrity of the motor cortex of the brain after a stroke.
Clinically, rTMS has been used to relieve depressive states. In the treatment of depression, 40 pulses of stimulation are delivered over four seconds, followed by a gap of 26 seconds before the next 40 pulses. A brain area called the left prefrontal cortex, which is in the front part of the brain, is targeted in this process.
Around 2,400-3,000 pulses are delivered in a single session, which may last for about 30 minutes. To achieve a clinical antidepressant effect, TMS is usually repeated daily for two to three weeks.
Recently, researchers have developed accelerated rTMS protocols. These treatment sessions last only for three minutes. Such protocols are also called intermittent theta burst stimulation (iTBS). The difference between standard rTMS and iTBS is in the speed of the delivered electromagnetic pulses. iTBS uses a three-minute protocol for clinical depression with a mix of high and low frequencies.
The iTBS protocol has also been modified to deliver a high dose. This was used in a 2021 clinical trial to treat people with treatment-resistant depression. Twenty-nine people with such depression participated in this trial. About half received a high-dose iTBS protocol and the rest received a placebo procedure that mimicked the real treatment. After five days of treatment, 79% of the participants in the treatment group were no longer depressed when evaluated on standard methods.
Research studies have also examined whether active and sham (dummy) TMS produce the same clinical response in depression. These studies concluded that greater response was observed in patients who received active treatment.
rTMS has also been used to treat refractory obsessive compulsive disorder (OCD). Although the FDA has approved the use of rTMS for refractory OCD, more evidence and refinement in protocols are needed at this time. At present, it remains an add-on treatment.
There is also preliminary evidence that rTMS relieves post-traumatic stress disorder (or PTSD).
Does TMS have adverse effects?
Rarely, rTMS may induce seizures in at-risk patients, for example those with a family history of epilepsy. This is more likely with fast rTMS than with slow rTMS. However, current safety protocols have also greatly reduced the likelihood of seizures.
Minor side-effects are more common, including muscle tension headaches. To prevent short-term changes in hearing threshold as a result of the noise generated by the equipment, earplugs are recommended during the session.
The field of non-invasive brain stimulation is rapidly expanding. This offers hope to millions who are clinically depressed. rTMS has proved to be a safe and efficacious brain stimulation modality in treating refractory depression.
Dr. Alok Kulkarni is a senior geriatric psychiatrist and neurophysician at the Manas Institute of Mental Health and Neurosciences, Hubli.
