Success in patients with major depression: For the first time, physicians stimulated patients' medial forebrain bundles

April 9, 2013, University of Bonn
The medial forebrain bundle is highlighted in green. Credit: Volker Arnd Coenen/Uni Freiburg

Researchers from the Bonn University Hospital implanted pacemaker electrodes into the medial forebrain bundle in the brains of patients suffering from major depression with amazing results: In six out of seven patients, symptoms improved both considerably and rapidly. The method of Deep Brain Stimulation had already been tested on various structures within the brain, but with clearly lesser effect. The results of this new study have now been published in the renowned international journal Biological Psychiatry.

After months of deep sadness, a first smile appears on a patient's face. For many years, she had suffered from major depression and tried to end her life several times. She had spent the past years mostly in a passive state on her couch; even watching TV was too much effort for her. Now this young woman has found her joie de vivre again, enjoys laughing and travelling. She and an additional six patients with participated in a study involving a novel method for addressing major depression at the Bonn University Hospital.

Considerable amelioration of depression within days

Prof. Dr. Volker Arnd Coenen, at the Department of Neurosurgery (Klinik und Poliklinik für Neurochirurgie), implanted electrodes into the medial forebrain bundles in the brains of subjects suffering from major depression with the electrodes being connected to a . The nerve cells were then stimulated by means of a weak electrical current, a method called Deep Brain Stimulation. In a matter of days, in six out of seven patients, symptoms such as anxiety, despondence, listlessness and joylessness had improved considerably. "Such sensational success both in terms of the strength of the effects, as well as the speed of the response has so far not been achieved with any other method," says Prof. Dr. Thomas E. Schläpfer from the Bonn University Hospital Department of Psychiatry und Psychotherapy (Bonner Uniklinik für Psychiatrie und Psychotherapie).

Central part of the reward circuit

The medial forebrain bundle is a bundle of nerve fibers running from the deep-seated limbic system to the prefrontal cortex. In a certain place, the bundle is particularly narrow because the individual nerve fibers lie close together. "This is exactly the location in which we can have maximum effect using a minimum of current," explains Prof. Coenen, who is now the new head of the Freiburg University Hospital's Department of Stereotactic and Functional Neurosurgery (Abteilung Stereotaktische und Funktionelle Neurochirurgie am Universitätsklinikum Freiburg). The medial forebrain bundle is a central part of a euphoria circuit belonging to the brain's reward system. What kind of effect stimulation exactly has on is not yet known. But it obviously changes metabolic activity in the different brain centers.

Success clearly increased over that of earlier studies

The researchers have already shown in several studies that deep shows an amazing and–given the severity of the symptoms– unexpected degree of amelioration of symptoms in major depression. In those studies, however, the physicians had not implanted the into the medial forebrain bundle but instead into the nucleus accumbens, another part of the brain's reward system. This had resulted in clear and sustainable improvements in about 50 percent of subjects. "But in this new study, our results were even much better," says Prof. Schläpfer. A clear improvement in complaints was found in 85 percent of patients, instead of the earlier 50 percent. In addition, stimulation was performed with lower current levels, and the effects showed within a few days, instead of after weeks.

Method's long-term success proven

"Obviously, we have now come closer to a critical structure within the brain that is responsible for major depression," says the psychiatrist from the Bonn University Hospital. Another cause for optimism among the group of physicians is that, since the study's completion, an eighth patient has also been treated successfully. The have been observed for a period of up to 18 month after the intervention. Prof. Schläpfer reports, "The anti-depressive effect of within the medial forebrain bundle has not decreased during this period." This clearly indicates that the effects are not temporary. This method gives those who suffer from reason to hope. However, it will take quite a bit of time for the new procedure to become part of standard therapy.

Explore further: Therapeutic approach for patients with severe depression

More information: Rapid Effects of Deep Brain Stimulation for Treatment Resistant Major Depression, Biological Psychiatry, DOI: 10.1016/j.biopsych.2013.01.034

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1 / 5 (1) Apr 09, 2013
I would be curious about the effect of TDCS that has this region in the main path of the current. An electrode placement with anode/cathode placed at the rear center of the head at the tip of the cerebellum and the cathode/anode placed low center on the forehead might be a good montage to begin an investigation.

If this effect could be obtained via external stimulation it would be available to many, many more sufferers than deep placement would allow.
not rated yet Apr 10, 2013
@dongateley that is not a bad idea, but the obvious potential problems with this are that surface electrodes have to penetrate deep into the subcortical structures and that this is a highly improbable approach to be able to accuratley and precisely hit the targets. Furthermore, in order to have surface electodes hit deep into the subcortical areas, the stimulator would have to be something far superior to tDCS and would be more in line with rTMS (which is being done). This however raises the possibility of seizure induction.

I presume, without reading the manuscript, that these patients had undergone failed ECT trials.

Furthermore, a double-blind placebo controlled (sham v. actual) crossover design is needed to elimiate biases associated with ths trial, so it is highly preliminary at best (which I'm sure the authors state, again I haven't read the manuscipt)
1 / 5 (1) Apr 10, 2013
I'm not sure from the article how accurate and precise things need to be. So long as the region of interest is receiving the stimulus it's not clear to what extent being more diffuse would lessen the effect. Also, the necessary current density in the region might be too high to achieve with a more diffuse path.

People are already reporting depression relief with other TDCS placement montages so I hope someone gives this one a look.
not rated yet Apr 14, 2013
All patients here have failed ECT trials in common.
1 / 5 (1) Apr 14, 2013
ECT and TDCS are very far removed from each other. Head and electricity is about all they have in common. I don't think you can extrapolate the results of one to the other.

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