closed-loop-neurostimulation-for-biomarker-driven-personalized

Closed-Loop Neurostimulation for Biomarker-Driven, Personalized Treatment of Major Depressive Disorder

Deep brain stimulation involves the administration of electrical stimulation to targeted brain regions for therapeutic benefit. In the context of major ...

University of California, San Francisco

What We've Got Here Is Failure to Communicate: Improving Interventional Psychiatry With Closed-Loop Stimulation.

Deep brain stimulation is a promising treatment for severe depression, but lack of efficacy in randomized trials raises questions regarding anatomical targeting. We implanted multi-site intracranial electrodes in a severely depressed patient and systematically assessed the acute response to focal electrical neuromodulation. We found an elaborate repertoire of distinctive emotional responses that were rapid in onset, reproducible, and context and state dependent. Results provide proof of concept for personalized, circuit-specific medicine in psychiatry.

State-dependent responses to intracranial brain stimulation in a patient with depression.

Deep brain stimulation is a promising treatment for neuropsychiatric conditions such as major depression. It could be optimized by identifying neural biomarkers that trigger therapy selectively when symptom severity is elevated. We developed an approach that first used multi-day intracranial electrophysiology and focal electrical stimulation to identify a personalized symptom-specific biomarker and a treatment location where stimulation improved symptoms. We then implanted a chronic deep brain sensing and stimulation device and implemented a biomarker-driven closed-loop therapy in an individual with depression. Closed-loop therapy resulted in a rapid and sustained improvement in depression. Future work is required to determine if the results and approach of this n-of-1 study generalize to a broader population.

Closed-loop neuromodulation in an individual with treatment-resistant depression.

Publisher Correction: State-dependent responses to intracranial brain stimulation in a patient with depression.

Psychiatric disorders are highly prevalent, often devastating diseases that negatively impact the lives of millions of people worldwide. Although their etiological and diagnostic heterogeneity has long challenged drug discovery, an emerging circuit-based understanding of psychiatric illness is offering an important alternative to the current reliance on trial and error, both in the development and in the clinical application of treatments. Here we review new and emerging treatment approaches, with a particular emphasis on the revolutionary potential of brain-circuit-based interventions for precision psychiatry. Limitations of circuit models, challenges of bringing precision therapeutics to market and the crucial advances needed to overcome these obstacles are presented.

Article	Year
What We've Got Here Is Failure to Communicate: Improving Interventional Psychiatry With Closed-Loop Stimulation. Biological psychiatry\| PubMed ID: 30261977	2018
State-dependent responses to intracranial brain stimulation in a patient with depression. Nature medicine\| PubMed ID: 33462446	2021
Closed-loop neuromodulation in an individual with treatment-resistant depression. Nature medicine\| PubMed ID: 34608328	2021
Publisher Correction: State-dependent responses to intracranial brain stimulation in a patient with depression. Nature medicine\| PubMed ID: 35941379	2022
New and emerging approaches to treat psychiatric disorders. Nature medicine\| PubMed ID: 36797480	2023

Katherine W. Scangos

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