Depression and deep brain stimulation therapy
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Closed-loop, deep brain stimulation (DBS) therapy has shown promising therapeutic effects in a small sample size, indicating the promise of customized, biomarker-driven neuromodulation for treatment-resistant depression. Katherine Scangos (University of California, San Francisco, USA) and colleagues reported their findings in Nature Medicine in a study that supports this theory.
To begin, Scangos et al note that DBS is a potential therapy option for neuropsychiatric diseases like major depression and that tailored techniques may assist to optimise this DBS indication further due to the complex, underlying neuronal circuits linked with depressive symptoms. Closed-loop neuromodulation, in which a patient’s own physiological activity is used to selectively initiate stimulation only when a given clinical state is detected, is another method of personalization.
Additional advantages of closed-loop stimulation include alleviating worries about brain adaptation and battery life, reducing side effects, and improving treatment success rates for depression. There is still a need for a biomarker specific to the symptoms of major depressive disorder in order to implement closed-loop therapy.
Among their findings is the discovery of a biomarker of major depressive symptoms during a 10-day period of intracranial corticolimbic circuitry mapping utilizing electrodes from the sEEG system, which they describe in their report (PMT Corporation). An FDA-approved RNS device (NeuroPace) was then implanted unilaterally in the patient’s right hemisphere, and closed-loop neuromodulation therapy was administered over the course of several months.
According to Scangos and colleagues, the daily HAMD-6 and VAS (visual analogue scale) symptoms of depression (as measured by the Six-item Hamilton depression rating scale [HAMD-6]) and symptom intensity reduced rapidly after the adoption of closed-loop therapy. In the initial assessment following 12 days of stimulation, the patient’s MADRS score went from 33 to 14 (remission), down from 33 before turning on the treatment. According to the authors, her HAMD-6 and VAS-D scores declined dramatically on the first day of stimulation and were lower in the next seven days than they were in the prior week.
The researchers used dynamic time warping (DTW) to nonlinearly align daily symptom severity (VAS-D) and biomarker detection count time traces over two months and calculated their relative post-alignment distance to see if their algorithm triggered stimulus delivery linked to patient symptoms and not randomly. They discovered that the number of biomarker events recognized by the device fluctuated considerably with the number of daily symptoms, suggesting that their biomarker identification method was significantly better than random chance at detecting variations in symptom severity.
A biomarker for depression-specific symptoms and closed-loop therapy for MDD [major depressive disorder] have been successfully developed and implemented, according to Scangos et al. Clinical mapping prior to chronic device placement, a strategy that has been used in epilepsy to map seizure foci in a tailored manner, but has not before been undertaken in other neuropsychiatric diseases, was the key to the success of this study.
During this stage, we created a multimodal framework for selecting brain targets to be sensed and stimulated. By combining resting-state signals with clinical symptoms, as well as functionally and structurally linked subnetworks across the corticolimbic network, our strategy includes individualized stimulus-response mapping.”
It’s not clear if this specific biomarker of sadness is present in all patients, and the authors acknowledge the study’s shortcomings, including its small sample size and the fact that doctors were not always blinded to stimulation sites or parameters. As a result, they note that the purpose of this study was not to investigate the efficacy of closed-loop neuromodulation for the treatment of MDD.
For neuropsychiatric illnesses, “we established proof-of-concept in our trial,” they conclude. Using the novel paradigm given in this article, researchers hope to advance neural interfaces based on biomarkers and gain a better knowledge of how various neurological disorders work.