Repetitive Transcranial Magnetic Stimulation: rTMS and Depression

Magnetic stimulation of the brain's left prefrontal cortex may help some depressed patients in much the same way as electro convulsive therapy (ECT), but without its side effects, suggests a preliminary study by Mark George, M.D., of the National Institute of Mental Health (NIMH), Eric Wassermann, M.D., National Institute on Neurological Disorders and Stroke (NINDS), and NIH colleagues.

They found that two of six medication-resistant patients showed marked mood improvement after treatment with repetitive Transcranial Magnetic Stimulation (rTMS) over several days. One of the two responders, a middle-aged woman, reported feeling well for the first time in three years. Two other patients experienced slight mood improvement and two no improvement following the experimental procedure, which employs an electromagnetic coil that induces a current in the brain's cortex.

The treatment is administered daily for at least a week, much like ECT, except that subjects remain awake. Although proven effective for depression, ECT entails risks associated with a seizure, occasional memory loss, and general anesthesia, which is required. In the pilot rTMS study, two patients developed mild headaches, treatable with aspirin -- the only reported side effects. However, rTMS does entail some risk, especially for seizure-prone individuals, and would not necessarily help all patients who respond to ECT.

Unlike electricity, which gets diffused by the skull, high intensity magnetic pulses pass readily through bone, making possible more focused targeting of particular brain structures. The NIMH investigators aimed the magnet at the brain's left prefrontal cortex, since it has been implicated as a site of abnormally low metabolism in studies of depression. PET (positron emission topography) scans performed in one patient during and after treatment showed widespread increases in metabolism, hinting that the magnet's effects may be broadly telegraphed via interconnected brain circuitry, suggests Dr. George. A controlled trial of rTMS for depression is currently underway at NIMH -- the first of a series required before its safety and efficacy can be established.

Researchers hope this and other work with magnetic stimulation will shed light on the mechanism of action of ECT, which remains a mystery. If magnetic pulses can produce an antidepressant effect, then the seizure that occurs in ECT may not be necessary.

Evidence is emerging from animal studies about how electrical currents, such as those induced in rTMS, might alter brain mechanisms. For example, NIMH's Susan Weiss, Ph.D., finds that low frequency electrical stimulation triggers lasting anticonvulsant effects in rats. Other investigators have found that magnetic stimulation produces an antidepressant effect in some animal models of depression.

In addition to its possible therapeutic potential, rTMS is also being used as a selective probe in studies of human brain function. For example, depending on where the coil is placed, it can disrupt speech or interfere with different types of memory. Investigators are also following up clues that it may trigger different emotional states in normal subjects, depending upon magnet placement.

rTMS and depression

Brain is the only target area of depression. rTMS has the potential to selectively modulate activity in those areas of brain, which are effected by depression. One of the determining factors in depression is a decrease in the levels of activity in the prefrontal cortex of the brain, particularly the left side of the brain. This area is readily accessible to the magnetic field and is highly interconnected with other structures that play a role in mood modulations and major depression. rTMS treats depression by inducing a current into the DLPFC with stimulation by a magnetic field. rTMS can alter activity in other remote areas of the brain structure even though they are not directly accessible to the rTMS coil. A process of focal cortial stimulation does this, and some of these remote brain structures are also believe to be linked to depression. The inaccessible areas of the brain are then stimulated, resulting in an indirect stimulation.

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