In deep brain stimulation or DBS, a neurostimulation device is surgically implanted in the brain and is used to modulate the activity of deep brain structures, targeting dysfunctional circuits associated with neuropsychiatric symptoms. The development of DBS has followed a decades-long history of psychiatric neurosurgery, with advances in pacemakers and spinal neurostimulation devices moving forward the use of DBS in the treatment of neuropsychiatric disorders.
Darin Dougherty, MD, Director of the Division of Neurotherapeutics at Mass General, and his colleagues have been pioneering and refining the use of DBS for the treatment of psychiatric disorders, including major depressive disorder (MDD) and obsessive-compulsive disorder (OCD), that have been resistant to conventional treatments. While numerous studies of DBS have reported significant improvements in patients with severe, treatment-resistant depression and OCD, the response rates in randomized controlled trials have been variable. Experts hypothesize that this inconsistency in response may reflect small but important differences in brain structure between individuals.
Dougherty’s team has been using advanced neuroimaging techniques to generate patient-specific brain maps that would ultimately improve the placement of electrodes used for DBS. At this point, the placement of electrodes in each individual uses the same stereotactic mapping targets in terms of x, y, z coordinates. Generating more refined, patient-specific targets which take individual anatomic variability into consideration is crucial to improving the efficacy of DBS, as the success of the procedure depends on the accurate placement of electrodes in specific brain regions.
Using Advanced Neuroimaging Techniques to Generate Patient-Specific Brain Maps
In order to improve brain mapping, Dougherty and researchers from the Psychiatric Neuroimaging Research Program have been mapping the human brain using a wide array of advanced imaging techniques and neurostimulation technologies. Dougherty and his team have emphasized a network-oriented approach to DBS. This perspective considers psychiatric disorders as arising from dysfunctions in brain networks rather than specific brain regions. By focusing more precisely on these networks, researchers aim to develop more effective and personalized DBS treatments.
In a recent study, the research team examined 534 deep brain stimulation electrodes implanted to treat four different brain disorders and analyzed which connections were associated with optimal therapeutic response for each disorder. They were able to identify specific dysfunctional circuits in the frontal cortex, topographically arranged from occipital to frontal. In individuals with OCD, dysfunctional circuits were mapped to the ventromedial prefrontal and anterior cingulate cortices.
A recent interview highlights the importance of creating personalized brain maps for each patient and how this can dramatically improve treatment outcomes. In one case, a young patient who had not responded to conventional DBS but experienced significant symptom relief after her stimulation protocol was adjusted based on a custom-made brain map. This approach allowed clinicians to identify and target specific neural pathways unique to her brain, underscoring the potential of personalized neurostimulation to transform the lives of those living with severe and disabling psychiatric disorders.
Next Steps: Improving the Efficacy of Deep Brain Stimulation
Currently, deep brain stimulation has been approved by the U.S. Food and Drug Administration for the treatment of intractable obsessive-compulsive disorder, through a Humanitarian Device Exemption. With more individualized identification of target areas, researchers hope to enhance the efficacy and safety of DBS and to use DBS to treat other psychiatric disorders, including treatment-resistant MDD.
The integration of advanced brain mapping techniques with deep brain stimulation represents a significant step forward in the treatment of refractory psychiatric disorders. By providing a more nuanced understanding of the neural circuits associated with a particular disorder, these approaches offer the potential for more targeted, individualized and effective interventions. By tailoring treatment to the individual’s unique brain structure and network dysfunctions, clinicians can achieve better outcomes and minimize adverse effects.
The development of adaptive, closed-loop DBS systems, which adjust stimulation parameters in real-time based on neural activity, have been a significant advance. These systems can provide more precise and adaptive treatment, potentially enhancing efficacy and reducing side effects.
As more patients receive DBS for OCD, it will be crucial to conduct long-term follow-up studies to assess the durability of treatment effects and identify any potential late-onset side effects. This information will be invaluable for refining patient selection criteria and optimizing long-term management strategies.
Mass General Brigham researchers involved in this project include Konstantin Butenko, Clemens Neudorfer, Matteo Vissani, Pranav Nanda, Darin Dougherty, R. Mark Richardson, and Andreas Horn.
Read More
Borron BM, Dougherty DD. Deep Brain Stimulation for Intractable Obsessive-Compulsive Disorder and Treatment-Resistant Depression. Focus (Am Psychiatr Publ). 2022 Jan; 20(1):55-63.
Hollunder B, Ostrem JL, Sahin IA, Rajamani N, Oxenford S, Butenko K, Neudorfer C, Reinhardt P, Zvarova P, Polosan M, Akram H, Vissani M, Zhang C, Sun B, Navratil P, Reich MM, Volkmann J, Yeh FC, Baldermann JC, Dembek TA, Visser-Vandewalle V, Alho EJL, Franceschini PR, Nanda P, Finke C, Kühn AA, Dougherty DD, Richardson RM, Bergman H, DeLong MR, Mazzoni A, Romito LM, Tyagi H, Zrinzo L, Joyce EM, Chabardes S, Starr PA, Li N, Horn A. Mapping dysfunctional circuits in the frontal cortex using deep brain stimulation. Nat Neurosci. 2024 Mar;27(3):573-586. doi: 10.1038/s41593-024-01570-1. Epub 2024 Feb 22. PMID: 38388734; PMCID: PMC10917675.
Meyer GM, Hollunder B, Li N, Butenko K, Dembek TA, Hart L, Nombela C, Mosley P, Akram H, Acevedo N, Borron BM, Chou T, Castaño Montoya JP, Strange B, Barcia JA, Tyagi H, Castle DJ, Smith AH, Choi KS, Kopell BH, Mayberg HS, Sheth SA, Goodman WK, Leentjens AFG, Richardson RM, Rossell SL, Bosanac P, Cosgrove GR, Kuhn J, Visser-Vandewalle V, Figee M, Dougherty DD, Siddiqi SH, Zrinzo L, Joyce E, Baldermann JC, Fox MD, Neudorfer C, Horn A. Deep Brain Stimulation for Obsessive-Compulsive Disorder: Optimal Stimulation Sites. Biol Psychiatry. 2024 Jul 15; 96(2):101-113.
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Deep Brain Stimulation Treatment Returns Hope to an Aspiring College Student (Mass General Brighman Patient Stories)
Deep brain stimulation didn’t work for a young OCD patient until new brain maps changed everything (CNN)
Darin Dougherty, MD is the Director of the Division of Neurotherapeutics in the Department of Psychiatry and is an Associate Professor of Psychiatry at Harvard Medical School. His research focuses on neurotherapeutic interventions for severe, treatment-resistant psychiatric illnesses, particularly for PTSD, eating disorders, major depressive disorder and obsessive compulsive disorder. His studies span both mechanistic studies, clinical trials, and device-based interventions employing a variety of techniques, including neuroimaging and electrophysiology. We also provide clinical services and surgical treatments for psychiatric illness.
