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expert reaction to a study using personalised brain stimulation for treatment-resistant depression in a single individual

A study published in Nature Medicine looks at the use of brain electrical stimulation for treatment-resistant depression.


Prof Jonathan Roiser, Professor of Neuroscience & Mental Health, University College London (UCL), said:

“Direct brain stimulation using implanted electrodes has previously shown mixed results in depression – this single case study tried a different approach. The key innovation was that the study team initially identified a specific region that seemed to be driving symptoms – the amygdala, which has previously been implicated in depression. They then implanted a device that continually sensed when amygdala activity was high, automatically activating a stimulator in a nearby connected region, the striatum, which turned off again when amygdala activity subsided. The patient experienced an immediate and dramatic reduction in symptoms, which was sustained over several months. Although this kind of highly invasive surgical procedure would only ever be used in the most severe patients with intractable symptoms, it is an exciting step forward due to the bespoke nature of the stimulation. It is likely that if trialled in other patients, different recording and stimulation sites would be required, as the precise brain circuitry underlying symptoms probably varies between individuals. As there was only one patient and no control condition, it remains to be seen whether these promising results hold in clinical trials.”


Prof Vladimir Litvak, Professor of Translational Neurophysiology, Wellcome Centre for Human Neuroimaging, University College London (UCL), said:

“This is an interesting study from one of the leading groups in the field. I find the press release quite accurate. The fact that in some patients, depression symptoms can be treated by electrical stimulation of the ventral striatum (a part of the brain’s reward and pleasure circuitry) is not new. What I find exciting is that the authors identified a particular neural activity pattern in the amygdala (a part of the brain that deals with response to threats) as a reliable predictor of both symptom severity and stimulation effectiveness. Patterns of brain activity correlated with disease symptoms when testing over a large group of patients are commonly discovered. But there are just a handful of examples of patterns that are reliable enough to be predictive on a short time scale in a single patient. Furthermore, to my knowledge, this is the first example of such a reliable biomarker for psychiatric symptoms. The other examples were all for neurological disorders such as Parkinson ’s disease, dystonia and epilepsy. I would treat a single case report with caution, but if this finding is reproduced in additional patients, it will bring at least some psychiatric conditions into the domain of brain diseases that can be characterised and diagnosed objectively rather than based on symptoms alone.

“Two additional key aspects of the study are the use of exploratory recordings and stimulation to determine the most effective treatment strategy and the use of a closed-loop device that only stimulates when detecting the amygdala biomarker. It is hard to say based on this single case how important these will be in the future. There is no comparison to constant stimulation that might have worked as well because the implanted device used in the study is not suitable for that.

“Implantation of multiple depth electrodes at different brain sites is a traumatic invasive procedure only reserved to date for severe cases of drug-resistant epilepsy. Furthermore, it only allows to test a small number of candidate sites so relies heavily on prior knowledge. Once clinicians know better what to look for, it might be possible to avoid this procedure altogether by using non-invasive methods (such as functional MRI or EEG) to match the right treatment option to a patient.”



‘Closed-loop neuromodulation in an individual with treatment-resistant depression’ by Katherine W. Scangos et al. was published in Nature Medicine at 16:00 UK time on Monday 4th October.




Declared interests

Prof Vladimir Litvak: “I am currently participating in a research funding application to search for electrophysiological biomarkers of depression symptoms using invasive recordings.”

None others received.


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