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1
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Trent ES, Zhou RJ, Mammo L, Goodman WK, Storch EA. High intensity approaches to exposure and response prevention for obsessive-compulsive disorder. Behav Brain Res 2025; 481:115427. [PMID: 39798884 DOI: 10.1016/j.bbr.2025.115427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 11/24/2024] [Accepted: 12/12/2024] [Indexed: 01/15/2025]
Abstract
Obsessive-compulsive disorder (OCD) is a debilitating psychiatric condition with multidetermined etiological and maintaining mechanisms. Cognitive behavioral therapy (CBT), specifically exposure and response prevention (ERP), is the first line behavioral intervention to treat OCD. ERP directly targets threat learning that characterizes OCD through processes of habituation (fear extinction) and inhibitory learning, in addition to eliciting neuronal changes implicated in OCD. Although ERP has a strong evidence base, not all OCD patients respond fully to standard, weekly or twice-weekly outpatient ERP. High intensity ERP-treatment delivered through more and/or longer sessions in a condensed manner-is a potential alternative approach that has also demonstrated efficacy for adults and youth with OCD. The goal of this review article is to describe the nature, rationale, and evidence for high intensity ERP for OCD treatment. We describe the foundations of ERP for OCD, various formats of intensive ERP, clinical research on the efficacy of this approach including neuronal changes, and potential pharmacological and neurosurgical augmentation strategies. We conclude with limitations of the current literature on intensive approaches and recommendations for future directions. While additional research is needed, high intensity ERP may be a promising approach for patients who have not responded to standard ERP or for patients requiring rapid symptom improvement.
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Affiliation(s)
- Erika S Trent
- Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, Houston, TX, United States.
| | - Robert J Zhou
- Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, Houston, TX, United States
| | - Liya Mammo
- Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, Houston, TX, United States
| | - Wayne K Goodman
- Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, Houston, TX, United States
| | - Eric A Storch
- Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, Houston, TX, United States
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2
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Kutscha N, Mahmutovic M, Bhusal B, Vu J, Chemlali C, Hansen SLJD, May MW, Knake S, Golestanirad L, Keil B. A deep brain stimulation-conditioned RF coil for 3T MRI. Magn Reson Med 2025; 93:1411-1426. [PMID: 39444303 DOI: 10.1002/mrm.30331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 08/20/2024] [Accepted: 09/19/2024] [Indexed: 10/25/2024]
Abstract
PURPOSE To develop and test an MRI coil assembly for imaging deep brain stimulation (DBS) at 3 T with a reduced level of local specific absorption rate of RF fields near the implant. METHODS A mechanical rotatable linearly polarized birdcage transmitter outfitted with a 32-channel receive array was constructed. The coil performance and image quality were systematically evaluated using bench-level measurements and imaging performance tests, including SNR maps, array element noise correlation, and acceleration capabilities. Electromagnetic simulations and phantom experiments were performed with clinically relevant DBS device configurations to evaluate the reduction of specific absorption rate and temperature near the implant compared with a circular polarized body coil setup. RESULTS The linearly polarized birdcage coil features a block-shaped low electric field region to be co-aligned with the implanted DBS lead trajectory, while the close-fit receive array enables imaging with high SNR and enhanced encoding capabilities. CONCLUSION The 3T coil assembly, consisting of a rotating linear birdcage and a 32-channel close-fit receive array, showed DBS-conditioned imaging technology with substantially reduced heat generation at the DBS implants.
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Affiliation(s)
- Nicolas Kutscha
- Institute of Medical Physics and Radiation Protection, Department of Life Science Engineering, TH-Mittelhessen University of Applied Sciences, Giessen, Germany
| | - Mirsad Mahmutovic
- Institute of Medical Physics and Radiation Protection, Department of Life Science Engineering, TH-Mittelhessen University of Applied Sciences, Giessen, Germany
| | - Bhumi Bhusal
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Jasmine Vu
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
- Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, Illinois, USA
| | - Chaimaa Chemlali
- Institute of Medical Physics and Radiation Protection, Department of Life Science Engineering, TH-Mittelhessen University of Applied Sciences, Giessen, Germany
| | - Sam-Luca J D Hansen
- Institute of Medical Physics and Radiation Protection, Department of Life Science Engineering, TH-Mittelhessen University of Applied Sciences, Giessen, Germany
| | - Markus W May
- Erwin L. Hahn Institute for Magnetic Resonance Imaging, University Duisburg-Essen, Essen, Germany
- High-Field and Hybrid MR Imaging, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Susanne Knake
- Department of Neurology, Philipps-Universität Marburg, Marburg, Germany
- Center for Mind, Brain and Behavior (CMBB), Universities of Marburg, Darmstadt, Germany
- LOEWE Research Cluster for Advanced Medical Physics in Imaging and Therapy (ADMIT), TH-Mittelhessen University of Applied Sciences, Giessen, Germany
| | - Laleh Golestanirad
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
- Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, Illinois, USA
| | - Boris Keil
- Institute of Medical Physics and Radiation Protection, Department of Life Science Engineering, TH-Mittelhessen University of Applied Sciences, Giessen, Germany
- Center for Mind, Brain and Behavior (CMBB), Universities of Marburg, Darmstadt, Germany
- LOEWE Research Cluster for Advanced Medical Physics in Imaging and Therapy (ADMIT), TH-Mittelhessen University of Applied Sciences, Giessen, Germany
- Department of Diagnostic and Interventional Radiology, University Hospital Marburg, Philipps-Universität Marburg, Marburg, Germany
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3
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Sahai E, Hickman J, Denman DJ. A Bioelectric Router for Adaptive Isochronous Neurostimulation. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.01.28.635122. [PMID: 39975050 PMCID: PMC11838292 DOI: 10.1101/2025.01.28.635122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
Objective Multipolar intracranial electrical brain stimulation (iEBS) is a method that has potential to improve clinical applications of mono- and bipolar iEBS. Current tools for researching multipolar iEBS are proprietary, can have high entry costs, lack flexibility in managing different stimulation parameters and electrodes, and can include clinical features unnecessary for the requisite exploratory research. This is a factor limiting the progress in understanding and applying multipolar iEBS effectively. To address these challenges, we developed the Bioelectric Router for Adaptive Isochronous Neuro stimulation (BRAINS) board. Approach The BRAINS board is a cost-effective and customizable device designed to facilitate multipolar stimulation experiments across a 16-channel electrode array using common research electrode setups. The BRAINS board interfaces with a microcontroller, allowing users to configure each channel for cathodal or anodal input, establish a grounded connection, or maintain a floating state. The design prioritizes ease of integration by leveraging standard tools like a microcontroller and an analog signal isolators while providing options to customize setups according to experimental conditions. It also ensures output isolation, reduces noise, and supports remote configuration changes for rapid switching of electrode states. To test the efficacy of the board, we performed bench-top validation of monopolar, bipolar, and multipolar stimulation regimes. The same regimes were tested in vivo in mouse primary visual cortex and measured using Neuropixel recordings. Main Results The BRAINS board demonstrates no meaningful differences in Root Mean Square Error (RMSE) noise or signal-to-noise ratio compared to the baseline performance of the isolated stimulator alone. The board supports configuration changes at a rate of up to 600 Hz without introducing residual noise, enabling high-frequency switching necessary for temporally multiplexed multipolar stimulation. Significance The BRAINS board represents a significant advancement in exploratory brain stimulation research by providing a user-friendly, customizable, open source, and cost-effective tool capable of conducting sophisticated, reproducible, and finely controlled stimulation experiments. With a capacity for effectively real-time information processing and efficient parameter exploration the BRAINS board can enhance both exploratory research on iEBS and enable improved clinical use of multipolar and closed-loop iEBS.
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Affiliation(s)
- Eashan Sahai
- University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Jordan Hickman
- University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Daniel J Denman
- University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
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4
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Naesström M, Blomstedt P, Johansson V. Deep Brain Stimulation in the Bed Nucleus of Stria Terminalis and Medial Forebrain Bundle in Two Patients With Treatment-Resistant Depression and Generalized Anxiety Disorder-A Long-Term Follow-Up. Clin Case Rep 2025; 13:e70179. [PMID: 39917375 PMCID: PMC11798865 DOI: 10.1002/ccr3.70179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 01/19/2025] [Accepted: 01/20/2025] [Indexed: 02/09/2025] Open
Abstract
This case report presents positive outcomes from deep brain stimulation (DBS) targeting the bed nucleus of the stria terminalis (BNST) in two patients with treatment-resistant depression and generalized anxiety disorder. DBS effects in the medial forebrain bundle (MFB) area were unclear. Further research into DBS's efficacy when comorbid anxiety is present is required.
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Affiliation(s)
- Matilda Naesström
- Department of Clinical Sciences, PsychiatryUmeå UniversityUmeåSweden
| | - Patric Blomstedt
- Department of Clinical Sciences, NeurosciencesUmeå UniversityUmeåSweden
| | - Viktoria Johansson
- Department of Clinical Sciences, PsychiatryUmeå UniversityUmeåSweden
- Centre for Pharmacoepidemiology, Department of Medicine SolnaKarolinska InstitutetStockholmSweden
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5
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Coffey RJ, Caroff SN. Neurosurgery for mental conditions and pain: An historical perspective on the limits of biological determinism. Surg Neurol Int 2024; 15:479. [PMID: 39777168 PMCID: PMC11705162 DOI: 10.25259/sni_819_2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Accepted: 11/26/2024] [Indexed: 01/11/2025] Open
Abstract
Neurosurgical operations treat involuntary movement disorders (MvDs), spasticity, cranial neuralgias, cancer pain, and other selected disorders, and implantable neurostimulation or drug delivery devices relieve MvDs, epilepsy, cancer pain, and spasticity. In contrast, studies of surgery or device implantations to treat chronic noncancer pain or mental conditions have not shown consistent evidence of efficacy and safety in formal, randomized, controlled trials. The success of particular operations in a finite set of disorders remains at odds with disconfirming results in others. Despite expectations that surgery or device implants would benefit particular patients, the normalization of unproven procedures could jeopardize the perceived legitimacy of functional neurosurgery in general. An unacknowledged challenge in functional neurosurgery is the limitation of biological determinism, wherein network activity is presumed to exclusively or predominantly mediate nociception, affect, and behavior. That notion regards certain pain states and mental conditions as disorders or dysregulation of networks, which, by implication, make them amenable to surgery. Moreover, implantable devices can now detect and analyze neural activity for observation outside the body, described as the extrinsic or micro perspective. This fosters a belief that automated analyses of physiological and imaging data can unburden the treatment of selected mental conditions and pain states from psychological subjectivity and complexity and the inherent sematic ambiguity of self-reporting. That idea is appealing; however, it discounts all other influences. Attempts to sway public opinion and regulators to approve deep brain stimulation for unproven indications could, if successful, harm the public interest, making demands for regulatory approval beside the point.
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Affiliation(s)
- Robert J. Coffey
- Medical Advisor, Retired. Medtronic, Inc., Neurological Division, Minneapolis, MN, United States
| | - Stanley N. Caroff
- Department of Psychiatry, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, United States
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6
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Sretavan K, Braun H, Liu Z, Bullock D, Palnitkar T, Patriat R, Chandrasekaran J, Brenny S, Johnson MD, Widge AS, Harel N, Heilbronner SR. A Reproducible Pipeline for Parcellation of the Anterior Limb of the Internal Capsule. BIOLOGICAL PSYCHIATRY. COGNITIVE NEUROSCIENCE AND NEUROIMAGING 2024; 9:1249-1261. [PMID: 39053578 DOI: 10.1016/j.bpsc.2024.07.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 07/11/2024] [Accepted: 07/11/2024] [Indexed: 07/27/2024]
Abstract
BACKGROUND The anterior limb of the internal capsule (ALIC) is a white matter structure that connects the prefrontal cortex (PFC) to the brainstem, thalamus, and subthalamic nucleus. It is a target for deep brain stimulation for obsessive-compulsive disorder. There is strong interest in improving deep brain stimulation targeting by using diffusion tractography to reconstruct and target specific ALIC fiber pathways, but this methodology is susceptible to errors and lacks validation. To address these limitations, we developed a novel diffusion tractography pipeline that generates reliable and biologically validated ALIC white matter reconstructions. METHODS Following algorithm development and refinement, we analyzed 43 control participants, each with 2 sets of 3T magnetic resonance imaging data and a subset of 5 control participants with 7T data from the Human Connectome Project. We generated 22 segmented ALIC fiber bundles (11 per hemisphere) based on PFC regions of interest, and we analyzed the relationships among bundles. RESULTS We successfully reproduced the topographies established by previous anatomical work using images acquired at both 3T and 7T. Quantitative assessment demonstrated significantly smaller intraparticipant variability than interparticipant variability for both test and retest groups across all but one PFC region. We examined the overlap between fibers from different PFC regions and a response tract for obsessive-compulsive disorder deep brain stimulation, and we reconstructed the PFC hyperdirect pathway using a modified version of our pipeline. CONCLUSIONS Our diffusion magnetic resonance imaging algorithm reliably generates biologically validated ALIC white matter reconstructions, thereby allowing for more precise modeling of fibers for neuromodulation therapies.
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Affiliation(s)
- Karianne Sretavan
- Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota; Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota
| | - Henry Braun
- Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota
| | - Zoe Liu
- Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota
| | - Daniel Bullock
- Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota
| | - Tara Palnitkar
- Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota
| | - Remi Patriat
- Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota
| | - Jayashree Chandrasekaran
- Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota
| | - Samuel Brenny
- Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota
| | - Matthew D Johnson
- Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota
| | - Alik S Widge
- Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota
| | - Noam Harel
- Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota; Department of Neurosurgery, University of Minnesota, Minneapolis, Minnesota
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Skandalakis GP, Neudorfer C, Payne CA, Bond E, Tavakkoli AD, Barrios-Martinez J, Trutti AC, Koutsarnakis C, Coenen VA, Komaitis S, Hadjipanayis CG, Stranjalis G, Yeh FC, Banihashemi L, Hong J, Lozano AM, Kogan M, Horn A, Evans LT, Kalyvas A. Establishing connectivity through microdissections of midbrain stimulation-related neural circuits. Brain 2024; 147:3083-3098. [PMID: 38808482 PMCID: PMC11370807 DOI: 10.1093/brain/awae173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 03/15/2024] [Accepted: 04/21/2024] [Indexed: 05/30/2024] Open
Abstract
Comprehensive understanding of the neural circuits involving the ventral tegmental area is essential for elucidating the anatomofunctional mechanisms governing human behaviour, in addition to the therapeutic and adverse effects of deep brain stimulation for neuropsychiatric diseases. Although the ventral tegmental area has been targeted successfully with deep brain stimulation for different neuropsychiatric diseases, the axonal connectivity of the region is not fully understood. Here, using fibre microdissections in human cadaveric hemispheres, population-based high-definition fibre tractography and previously reported deep brain stimulation hotspots, we find that the ventral tegmental area participates in an intricate network involving the serotonergic pontine nuclei, basal ganglia, limbic system, basal forebrain and prefrontal cortex, which is implicated in the treatment of obsessive-compulsive disorder, major depressive disorder, Alzheimer's disease, cluster headaches and aggressive behaviours.
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Affiliation(s)
- Georgios P Skandalakis
- Section of Neurosurgery, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA
- Department of Neurosurgery, National and Kapodistrian University of Athens Medical School, Evangelismos General Hospital, Athens 10676, Greece
| | - Clemens Neudorfer
- Center for Brain Circuit Therapeutics Department of Neurology Brigham & Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
- MGH Neurosurgery & Center for Neurotechnology and Neurorecovery (CNTR) at MGH Neurology Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
- Movement Disorder and Neuromodulation Unit, Department of Neurology, Department of Neurology, Charité—Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
| | - Caitlin A Payne
- Section of Neurosurgery, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA
| | - Evalina Bond
- Section of Neurosurgery, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA
| | - Armin D Tavakkoli
- Section of Neurosurgery, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA
| | | | - Anne C Trutti
- Integrative Model-Based Cognitive Neuroscience Research Unit, University of Amsterdam, Amsterdam 15926, The Netherlands
| | - Christos Koutsarnakis
- Department of Neurosurgery, National and Kapodistrian University of Athens Medical School, Evangelismos General Hospital, Athens 10676, Greece
| | - Volker A Coenen
- Department of Stereotactic and Functional Neurosurgery, Medical Center of the University of Freiburg, Freiburg 79106, Germany
- Medical Faculty of the University of Freiburg, Freiburg 79110, Germany
- Center for Deep Brain Stimulation, Medical Center of the University of Freiburg, Freiburg 79106, Germany
| | - Spyridon Komaitis
- Queens Medical Center, Nottingham University Hospitals NHS Foundation Trust, Nottingham NG7 2UH, UK
| | | | - George Stranjalis
- Department of Neurosurgery, National and Kapodistrian University of Athens Medical School, Evangelismos General Hospital, Athens 10676, Greece
| | - Fang-Cheng Yeh
- Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Layla Banihashemi
- Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Jennifer Hong
- Section of Neurosurgery, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA
| | - Andres M Lozano
- Division of Neurosurgery, University Health Network, University of Toronto, Toronto, ON M5T 1P5, Canada
| | - Michael Kogan
- Department of Neurosurgery, University of New Mexico School of Medicine, Albuquerque, NM 87106, USA
| | - Andreas Horn
- Center for Brain Circuit Therapeutics Department of Neurology Brigham & Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
- MGH Neurosurgery & Center for Neurotechnology and Neurorecovery (CNTR) at MGH Neurology Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
- Movement Disorder and Neuromodulation Unit, Department of Neurology, Department of Neurology, Charité—Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
| | - Linton T Evans
- Section of Neurosurgery, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA
| | - Aristotelis Kalyvas
- Division of Neurosurgery, University Health Network, University of Toronto, Toronto, ON M5T 1P5, Canada
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8
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Huang Y, Yao K, Zhang Q, Huang X, Chen Z, Zhou Y, Yu X. Bioelectronics for electrical stimulation: materials, devices and biomedical applications. Chem Soc Rev 2024; 53:8632-8712. [PMID: 39132912 DOI: 10.1039/d4cs00413b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/13/2024]
Abstract
Bioelectronics is a hot research topic, yet an important tool, as it facilitates the creation of advanced medical devices that interact with biological systems to effectively diagnose, monitor and treat a broad spectrum of health conditions. Electrical stimulation (ES) is a pivotal technique in bioelectronics, offering a precise, non-pharmacological means to modulate and control biological processes across molecular, cellular, tissue, and organ levels. This method holds the potential to restore or enhance physiological functions compromised by diseases or injuries by integrating sophisticated electrical signals, device interfaces, and designs tailored to specific biological mechanisms. This review explains the mechanisms by which ES influences cellular behaviors, introduces the essential stimulation principles, discusses the performance requirements for optimal ES systems, and highlights the representative applications. From this review, we can realize the potential of ES based bioelectronics in therapy, regenerative medicine and rehabilitation engineering technologies, ranging from tissue engineering to neurological technologies, and the modulation of cardiovascular and cognitive functions. This review underscores the versatility of ES in various biomedical contexts and emphasizes the need to adapt to complex biological and clinical landscapes it addresses.
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Affiliation(s)
- Ya Huang
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
| | - Kuanming Yao
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
| | - Qiang Zhang
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
| | - Xingcan Huang
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
| | - Zhenlin Chen
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
| | - Yu Zhou
- Department of Electronic and Computer Engineering, The Hong Kong University of Science and Technology, Hong Kong, China.
| | - Xinge Yu
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
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9
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Younus S, Havel L, Stiede JT, Rast CE, Saxena K, Goodman WK, Storch EA. Pediatric Treatment-Resistant Obsessive Compulsive Disorder: Treatment Options and Challenges. Paediatr Drugs 2024; 26:397-409. [PMID: 38877303 DOI: 10.1007/s40272-024-00639-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/22/2024] [Indexed: 06/16/2024]
Abstract
Pediatric obsessive-compulsive disorder (OCD) is a chronic, potentially debilitating psychiatric condition. Although effective treatments exist, at least 10% of youth do not achieve remission despite receiving first-line treatments. This article reviews the extant, albeit limited, evidence supporting treatment approaches for youth with treatment-resistant OCD. A literature search for articles addressing pediatric treatment-resistant OCD was conducted through April 11, 2024. These results were augmented by searching for treatment-resistant OCD in adults; treatment strategies discovered for the adult population were then searched in the context of children and adolescents. In general, intensive treatment programs and antipsychotic augmentation of an antidepressant had the most substantial and consistent evidence base for treatment-resistant youth with OCD, although studies were limited and of relatively poor methodological quality (i.e., open trials, naturalistic studies). Several pharmacological approaches (clomipramine, antipsychotics [e.g., aripiprazole, risperidone], riluzole, ketamine, D-cycloserine, memantine, topiramate, N-acetylcysteine, ondansetron), largely based on supporting data among adults, have received varying levels of investigation and support. There is nascent support for how to treat pediatric treatment-resistant OCD. Future treatment studies need to consider how to manage the significant minority of youth who fail to benefit from first-line treatment approaches.
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Affiliation(s)
- Sana Younus
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, 1977 Butler Blvd, Suite 4-400, Houston, TX, 77030, USA
- Texas Children's Hospital, Houston, TX, USA
| | - Lauren Havel
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, 1977 Butler Blvd, Suite 4-400, Houston, TX, 77030, USA
- Texas Children's Hospital, Houston, TX, USA
| | - Jordan T Stiede
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, 1977 Butler Blvd, Suite 4-400, Houston, TX, 77030, USA
| | - Catherine E Rast
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, 1977 Butler Blvd, Suite 4-400, Houston, TX, 77030, USA
| | - Kirti Saxena
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, 1977 Butler Blvd, Suite 4-400, Houston, TX, 77030, USA
- Texas Children's Hospital, Houston, TX, USA
| | - Wayne K Goodman
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, 1977 Butler Blvd, Suite 4-400, Houston, TX, 77030, USA
| | - Eric A Storch
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, 1977 Butler Blvd, Suite 4-400, Houston, TX, 77030, USA.
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10
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Zhang KK, Matin R, Gorodetsky C, Ibrahim GM, Gouveia FV. Systematic review of rodent studies of deep brain stimulation for the treatment of neurological, developmental and neuropsychiatric disorders. Transl Psychiatry 2024; 14:186. [PMID: 38605027 PMCID: PMC11009311 DOI: 10.1038/s41398-023-02727-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 12/19/2023] [Accepted: 12/22/2023] [Indexed: 04/13/2024] Open
Abstract
Deep brain stimulation (DBS) modulates local and widespread connectivity in dysfunctional networks. Positive results are observed in several patient populations; however, the precise mechanisms underlying treatment remain unknown. Translational DBS studies aim to answer these questions and provide knowledge for advancing the field. Here, we systematically review the literature on DBS studies involving models of neurological, developmental and neuropsychiatric disorders to provide a synthesis of the current scientific landscape surrounding this topic. A systematic analysis of the literature was performed following PRISMA guidelines. 407 original articles were included. Data extraction focused on study characteristics, including stimulation protocol, behavioural outcomes, and mechanisms of action. The number of articles published increased over the years, including 16 rat models and 13 mouse models of transgenic or healthy animals exposed to external factors to induce symptoms. Most studies targeted telencephalic structures with varying stimulation settings. Positive behavioural outcomes were reported in 85.8% of the included studies. In models of psychiatric and neurodevelopmental disorders, DBS-induced effects were associated with changes in monoamines and neuronal activity along the mesocorticolimbic circuit. For movement disorders, DBS improves symptoms via modulation of the striatal dopaminergic system. In dementia and epilepsy models, changes to cellular and molecular aspects of the hippocampus were shown to underlie symptom improvement. Despite limitations in translating findings from preclinical to clinical settings, rodent studies have contributed substantially to our current knowledge of the pathophysiology of disease and DBS mechanisms. Direct inhibition/excitation of neural activity, whereby DBS modulates pathological oscillatory activity within brain networks, is among the major theories of its mechanism. However, there remain fundamental questions on mechanisms, optimal targets and parameters that need to be better understood to improve this therapy and provide more individualized treatment according to the patient's predominant symptoms.
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Affiliation(s)
- Kristina K Zhang
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Program in Neuroscience and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada
| | - Rafi Matin
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Program in Neuroscience and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada
| | | | - George M Ibrahim
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Program in Neuroscience and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada
- Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada
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Patrick EE, Fleeting CR, Patel DR, Casauay JT, Patel A, Shepherd H, Wong JK. Modeling the volume of tissue activated in deep brain stimulation and its clinical influence: a review. Front Hum Neurosci 2024; 18:1333183. [PMID: 38660012 PMCID: PMC11039793 DOI: 10.3389/fnhum.2024.1333183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Accepted: 03/26/2024] [Indexed: 04/26/2024] Open
Abstract
Deep brain stimulation (DBS) is a neuromodulatory therapy that has been FDA approved for the treatment of various disorders, including but not limited to, movement disorders (e.g., Parkinson's disease and essential tremor), epilepsy, and obsessive-compulsive disorder. Computational methods for estimating the volume of tissue activated (VTA), coupled with brain imaging techniques, form the basis of models that are being generated from retrospective clinical studies for predicting DBS patient outcomes. For instance, VTA models are used to generate target-and network-based probabilistic stimulation maps that play a crucial role in predicting DBS treatment outcomes. This review defines the methods for calculation of tissue activation (or modulation) including ones that use heuristic and clinically derived estimates and more computationally involved ones that rely on finite-element methods and biophysical axon models. We define model parameters and provide a comparison of commercial, open-source, and academic simulation platforms available for integrated neuroimaging and neural activation prediction. In addition, we review clinical studies that use these modeling methods as a function of disease. By describing the tissue-activation modeling methods and highlighting their application in clinical studies, we provide the neural engineering and clinical neuromodulation communities with perspectives that may influence the adoption of modeling methods for future DBS studies.
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Affiliation(s)
- Erin E. Patrick
- Department of Electrical and Computer Engineering, University of Florida, Gainesville, FL, United States
| | - Chance R. Fleeting
- College of Medicine, University of Florida, Gainesville, FL, United States
| | - Drashti R. Patel
- College of Medicine, University of Florida, Gainesville, FL, United States
| | - Jed T. Casauay
- College of Medicine, University of Florida, Gainesville, FL, United States
| | - Aashay Patel
- College of Medicine, University of Florida, Gainesville, FL, United States
| | - Hunter Shepherd
- College of Medicine, University of Florida, Gainesville, FL, United States
| | - Joshua K. Wong
- Department of Neurology, Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, United States
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12
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Ranjan M, Mahoney JJ, Rezai AR. Neurosurgical neuromodulation therapy for psychiatric disorders. Neurotherapeutics 2024; 21:e00366. [PMID: 38688105 PMCID: PMC11070709 DOI: 10.1016/j.neurot.2024.e00366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 04/09/2024] [Accepted: 04/16/2024] [Indexed: 05/02/2024] Open
Abstract
Psychiatric disorders are among the leading contributors to global disease burden and disability. A significant portion of patients with psychiatric disorders remain treatment-refractory to best available therapy. With insights from the neurocircuitry of psychiatric disorders and extensive experience of neuromodulation with deep brain stimulation (DBS) in movement disorders, DBS is increasingly being considered to modulate the neural network in psychiatric disorders. Currently, obsessive-compulsive disorder (OCD) is the only U.S. FDA (United States Food and Drug Administration) approved DBS indication for psychiatric disorders. Medically refractory depression, addiction, and other psychiatric disorders are being explored for DBS neuromodulation. Studies evaluating DBS for psychiatric disorders are promising but lack larger, controlled studies. This paper presents a brief review and the current state of DBS and other neurosurgical neuromodulation therapies for OCD and other psychiatric disorders. We also present a brief review of MR-guided Focused Ultrasound (MRgFUS), a novel form of neurosurgical neuromodulation, which can target deep subcortical structures similar to DBS, but in a noninvasive fashion. Early experiences of neurosurgical neuromodulation therapies, including MRgFUS neuromodulation are encouraging in psychiatric disorders; however, they remain investigational. Currently, DBS and VNS are the only FDA approved neurosurgical neuromodulation options in properly selected cases of OCD and depression, respectively.
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Affiliation(s)
- Manish Ranjan
- Department of Neurosurgery, WVU Rockefeller Neuroscience Institute, Morgantown, WV, USA.
| | - James J Mahoney
- Department of Behavioral Medicine and Psychiatry, WVU Rockefeller Neuroscience Institute, Morgantown, WV, USA; Department of Neuroscience, WVU Rockefeller Neuroscience Institute, Morgantown, WV, USA
| | - Ali R Rezai
- Department of Neurosurgery, WVU Rockefeller Neuroscience Institute, Morgantown, WV, USA; Department of Neuroscience, WVU Rockefeller Neuroscience Institute, Morgantown, WV, USA
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13
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Unadkat P, Quevedo J, Soares J, Fenoy A. Opportunities and challenges for the use of deep brain stimulation in the treatment of refractory major depression. DISCOVER MENTAL HEALTH 2024; 4:9. [PMID: 38483709 PMCID: PMC10940557 DOI: 10.1007/s44192-024-00062-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 03/08/2024] [Indexed: 03/17/2024]
Abstract
Major Depressive Disorder continues to remain one of the most prevalent psychiatric diseases globally. Despite multiple trials of conventional therapies, a subset of patients fail to have adequate benefit to treatment. Deep brain stimulation (DBS) is a promising treatment in this difficult to treat population and has shown strong antidepressant effects across multiple cohorts. Nearly two decades of work have provided insights into the potential for chronic focal stimulation in precise brain targets to modulate pathological brain circuits that are implicated in the pathogenesis of depression. In this paper we review the rationale that prompted the selection of various brain targets for DBS, their subsequent clinical outcomes and common adverse events reported. We additionally discuss some of the pitfalls and challenges that have prevented more widespread adoption of this technology as well as future directions that have shown promise in improving therapeutic efficacy of DBS in the treatment of depression.
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Affiliation(s)
- Prashin Unadkat
- Elmezzi Graduate School of Molecular Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA
- Department of Neurosurgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, Hempstead, NY, USA
| | - Joao Quevedo
- Center of Excellence On Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, (UT Health), Houston, TX, USA
| | - Jair Soares
- Center of Excellence On Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, (UT Health), Houston, TX, USA
| | - Albert Fenoy
- Elmezzi Graduate School of Molecular Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.
- Department of Neurosurgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, Hempstead, NY, USA.
- Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.
- Department of Psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, Hempstead, NY, USA.
- Department of Neurosurgery, Donald and Barbara Zucker School of Medicine, Feinstein Institutes for Medical Research, Northwell Health, 805 Northern Boulevard, Suite 100, Great Neck, NY, 11021, USA.
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14
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Germann J, Gouveia FV, Beyn ME, Elias GJB, Lozano AM. Computational Neurosurgery in Deep Brain Stimulation. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1462:435-451. [PMID: 39523281 DOI: 10.1007/978-3-031-64892-2_26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
Computational methods and technologies are critical for neurosurgery in general and in deep brain stimulation (DBS) in particular. They increasingly inform every aspect of clinical DBS therapy, from presurgical planning and hardware implantation to postoperative adjustment of stimulation parameters. Computational methods also occupy a prominent position within the DBS research sphere, where they facilitate efforts to better understand DBS' underlying mechanisms and optimize and individualize its delivery. This chapter provides a high-level overview of the various computational tools and methods that have been applied to DBS. First, we discuss the invaluable contribution of computational neuroimaging (primarily magnetic resonance imaging) to DBS, targeting and the role of postoperative methods of image analysis-specifically, electrode localization, volume of activated tissue modeling, and sweet-spot mapping-in precisely localizing DBS' targets in the brain and discerning optimal treatment loci. We then address the growing field of connectomics, which leverages specific magnetic resonance imaging (MRI) sequences and post-acquisition processing algorithms to explore how DBS operates at the level of brain-wide networks. Next, the search for electrophysiological and imaging-based biomarkers of optimal DBS therapy is explored. We lastly touch on the incipient field of spatial characterization analysis and discuss the ongoing development of adaptive, closed-loop DBS systems.
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Affiliation(s)
- Jürgen Germann
- Division of Neurosurgery, Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada
- Krembil Brain Institute, Toronto Western Hospital, University Health Network, Toronto, ON, Canada
| | | | - Michelle E Beyn
- Division of Neurosurgery, Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Gavin J B Elias
- Division of Neurosurgery, Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Andres M Lozano
- Division of Neurosurgery, Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada.
- Krembil Brain Institute, Toronto Western Hospital, University Health Network, Toronto, ON, Canada.
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15
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Chan JL, Carpentier AV, Middlebrooks EH, Okun MS, Wong JK. Current perspectives on tractography-guided deep brain stimulation for the treatment of mood disorders. Expert Rev Neurother 2024; 24:11-24. [PMID: 38037329 DOI: 10.1080/14737175.2023.2289573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Accepted: 11/27/2023] [Indexed: 12/02/2023]
Abstract
INTRODUCTION Deep brain stimulation (DBS) is an emerging therapy for mood disorders, particularly treatment-resistant depression (TRD). Different brain areas implicated in depression-related brain networks have been investigated as DBS targets and variable clinical outcomes highlight the importance of target identification. Tractography has provided insight into how DBS modulates disorder-related brain networks and is being increasingly used to guide DBS for psychiatric disorders. AREAS COVERED In this perspective, an overview of the current state of DBS for TRD and the principles of tractography is provided. Next, a comprehensive review of DBS targets is presented with a focus on tractography. Finally, the challenges and future directions of tractography-guided DBS are discussed. EXPERT OPINION Tractography-guided DBS is a promising tool for improving DBS outcomes for mood disorders. Tractography is particularly useful for targeting patient-specific white matter tracts that are not visible using conventional structural MRI. Developments in tractography methods will help refine DBS targeting for TRD and may facilitate symptom-specific precision neuromodulation. Ultimately, the standardization of tractography methods will be essential to transforming DBS into an established therapy for mood disorders.
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Affiliation(s)
- Jason L Chan
- Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida, USA
- Department of Neurology, University of Florida, Gainesville, Florida, USA
| | - Ariane V Carpentier
- Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida, USA
- Department of Neurology, University of Florida, Gainesville, Florida, USA
| | | | - Michael S Okun
- Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida, USA
- Department of Neurology, University of Florida, Gainesville, Florida, USA
| | - Joshua K Wong
- Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida, USA
- Department of Neurology, University of Florida, Gainesville, Florida, USA
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16
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Silemek B, Seifert F, Petzold J, Brühl R, Ittermann B, Winter L. Wirelessly interfacing sensor-equipped implants and MR scanners for improved safety and imaging. Magn Reson Med 2023; 90:2608-2626. [PMID: 37533167 DOI: 10.1002/mrm.29818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 07/12/2023] [Accepted: 07/13/2023] [Indexed: 08/04/2023]
Abstract
PURPOSE To investigate a novel reduced RF heating method for imaging in the presence of active implanted medical devices (AIMDs) which employs a sensor-equipped implant that provides wireless feedback. METHODS The implant, consisting of a generator case and a lead, measures RF-inducedE $$ E $$ -fields at the implant tip using a simple sensor in the generator case and transmits these values wirelessly to the MR scanner. Based on the sensor signal alone, parallel transmission (pTx) excitation vectors were calculated to suppress tip heating and maintain image quality. A sensor-based imaging metric was introduced to assess the image quality. The methodology was studied at 7T in testbed experiments, and at a 3T scanner in an ASTM phantom containing AIMDs instrumented with six realistic deep brain stimulation (DBS) lead configurations adapted from patients. RESULTS The implant successfully measured RF-inducedE $$ E $$ -fields (Pearson correlation coefficient squared [R2 ] = 0.93) and temperature rises (R2 = 0.95) at the implant tip. The implant acquired the relevant data needed to calculate the pTx excitation vectors and transmitted them wirelessly to the MR scanner within a single shot RF sequence (<60 ms). Temperature rises for six realistic DBS lead configurations were reduced to 0.03-0.14 K for heating suppression modes compared to 0.52-3.33 K for the worst-case heating, while imaging quality remained comparable (five of six lead imaging scores were ≥0.80/1.00) to conventional circular polarization (CP) images. CONCLUSION Implants with sensors that can communicate with an MR scanner can substantially improve safety for patients in a fast and automated manner, easing the current burden for MR personnel.
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Affiliation(s)
- Berk Silemek
- Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Germany
| | - Frank Seifert
- Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Germany
| | - Johannes Petzold
- Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Germany
| | - Rüdiger Brühl
- Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Germany
| | - Bernd Ittermann
- Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Germany
| | - Lukas Winter
- Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Germany
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17
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Kamble SR, Dandekar MP. Implication of microbiota gut-brain axis in the manifestation of obsessive-compulsive disorder: Preclinical and clinical evidence. Eur J Pharmacol 2023; 957:176014. [PMID: 37619786 DOI: 10.1016/j.ejphar.2023.176014] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 08/21/2023] [Accepted: 08/22/2023] [Indexed: 08/26/2023]
Abstract
Recent research has highlighted the key role of gut microbiota in the development of psychiatric disorders. The adverse impact of stress, anxiety, and depression has been well documented on the commensal gut microflora. Thus, therapeutic benefits of gut microbiota-based interventions may not be avoided in central nervous system (CNS) disorders. In this review, we outline the current state of knowledge of gut microbiota with respect to obsessive-compulsive disorder (OCD). We discuss how OCD-generated changes corresponding to the key neurotransmitters, hypothalamic-pituitary-adrenal axis, and immunological and inflammatory pathways are connected with the modifications of the microbiota-gut-brain axis. Notably, administration of few probiotics such as Lactobacillus rhamnosus (ATCC 53103), Lactobacillus helveticus R0052, Bifidobacterium longum R0175, Saccharomyces boulardii, and Lactobacillus casei Shirota imparted positive effects in the management of OCD symptoms. Taken together, we suggest that the gut microbiota-directed therapeutics may open new treatment approaches for the management of OCD.
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Affiliation(s)
- Sonali R Kamble
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
| | - Manoj P Dandekar
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India.
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18
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Acevedo N, Castle DJ, Bosanac P, Rossell SL. Call to revise the Royal Australian and New Zealand College of Psychiatrists' clinical memorandum on deep brain stimulation for obsessive-compulsive disorder. Aust N Z J Psychiatry 2023; 57:1304-1307. [PMID: 37395129 PMCID: PMC10517578 DOI: 10.1177/00048674231184410] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/04/2023]
Affiliation(s)
- Nicola Acevedo
- Centre for Mental Health, Swinburne University of Technology, Melbourne, VIC, Australia
- Department of Psychiatry, St Vincent’s Hospital, Melbourne, VIC, Australia
| | | | - Peter Bosanac
- Department of Psychiatry, St Vincent’s Hospital, Melbourne, VIC, Australia
- Department of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia
| | - Susan L Rossell
- Centre for Mental Health, Swinburne University of Technology, Melbourne, VIC, Australia
- Department of Psychiatry, St Vincent’s Hospital, Melbourne, VIC, Australia
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19
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Abdelnaim MA, Lang-Hambauer V, Hebel T, Schoisswohl S, Schecklmann M, Deuter D, Schlaier J, Langguth B. Deep brain stimulation for treatment resistant obsessive compulsive disorder; an observational study with ten patients under real-life conditions. Front Psychiatry 2023; 14:1242566. [PMID: 37779611 PMCID: PMC10533930 DOI: 10.3389/fpsyt.2023.1242566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Accepted: 08/23/2023] [Indexed: 10/03/2023] Open
Abstract
Introduction Obsessive-compulsive disorder (OCD) affects 2-3% of the global population, causing distress in many functioning levels. Standard treatments only lead to a partial recovery, and about 10% of the patients remain treatment-resistant. Deep brain stimulation offers a treatment option for severe, therapy-refractory OCD, with a reported response of about 60%. We report a comprehensive clinical, demographic, and treatment data for patients who were treated with DBS in our institution. Methods We offered DBS to patients with severe chronic treatment resistant OCD. Severity was defined as marked impairment in functioning and treatment resistance was defined as non-response to adequate trials of medications and psychotherapy. Between 2020 and 2022, 11 patients were implanted bilaterally in the bed nucleus of stria terminalis (BNST). Patients were evaluated with YBOCS, MADRS, GAF, CGI, and WHOQOL-BREF. We performed the ratings at baseline (before surgery), after implantation before the start of the stimulation, after reaching satisfactory stimulation parameters, and at follow-up visits 3, 6, 9, and 12 months after optimized stimulation. Results One patient has retracted his consent to publish the results of his treatment, thus we are reporting the results of 10 patients (5 males, 5 females, mean age: 37 years). Out of our 10 patients, 6 have shown a clear response indicated by a YBOCS-reduction between 42 and 100 percent at last follow-up. One further patient experienced a subjectively dramatic effect on OCD symptoms, but opted afterwards to stop the stimulation. The other 3 patients showed a slight, non-significant improvement of YBOCS between 8.8 and 21.9%. The overall mean YBOCS decreased from 28.3 at baseline to 13.3 (53% reduction) at the last follow-up. The improvement of the OCD symptoms was also accompanied by an improvement of depressive symptoms, global functioning, and quality of life. Conclusion Our results suggest that BNST-DBS can be effective for treatment-resistant OCD patients, as indicated by a reduction in symptoms and an overall improvement in functioning. Despite the need for additional research to define the patients' selection criteria, the most appropriate anatomical target, and the most effective stimulation parameters, improved patient access for this therapy should be established.
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Affiliation(s)
- Mohamed A. Abdelnaim
- Department of Psychiatry and Psychotherapy, University Regensburg, Regensburg, Germany
- Center for Deep Brain Stimulation, University Regensburg, Regensburg, Germany
| | - Verena Lang-Hambauer
- Department of Psychiatry and Psychotherapy, University Regensburg, Regensburg, Germany
- Center for Deep Brain Stimulation, University Regensburg, Regensburg, Germany
| | - Tobias Hebel
- Department of Psychiatry and Psychotherapy, University Regensburg, Regensburg, Germany
| | - Stefan Schoisswohl
- Department of Psychiatry and Psychotherapy, University Regensburg, Regensburg, Germany
- Department of Psychology, University of the Bundeswehr Munich, Neubiberg, Germany
| | - Martin Schecklmann
- Department of Psychiatry and Psychotherapy, University Regensburg, Regensburg, Germany
| | - Daniel Deuter
- Center for Deep Brain Stimulation, University Regensburg, Regensburg, Germany
- Department of Neurosurgery, University Regensburg, Regensburg, Germany
| | - Juergen Schlaier
- Center for Deep Brain Stimulation, University Regensburg, Regensburg, Germany
- Department of Neurosurgery, University Regensburg, Regensburg, Germany
| | - Berthold Langguth
- Department of Psychiatry and Psychotherapy, University Regensburg, Regensburg, Germany
- Center for Deep Brain Stimulation, University Regensburg, Regensburg, Germany
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20
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Shaheen N, Shaheen A, Sarica C, Singh A, Zanaty M, Johari K, Yang A, Zesiewicz T, Dalm B, Bezchlibnyk Y, Lozano AM, Flouty O. Deep brain stimulation for substance use disorder: a systematic review and meta-analysis. Front Psychiatry 2023; 14:1231760. [PMID: 37636824 PMCID: PMC10449586 DOI: 10.3389/fpsyt.2023.1231760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 07/25/2023] [Indexed: 08/29/2023] Open
Abstract
Objective Substance use disorder (SUD) is a significant public health issue with a high mortality rate. Deep brain stimulation (DBS) has shown promising results in treating SUD in certain cases. In this study, we conducted a meta-analysis to evaluate the efficacy of DBS in the treatment of SUD and reduction of relapse rates. Methods We performed a thorough and methodical search of the existing scientific literature, adhering to the PRISMA guidelines, to identify 16 original studies that fulfilled our inclusion criteria. We used the evidence levels recommended by the Oxford Centre for Evidence-Based Medicine to assess bias. The R version 4.2.3 software was utilized to calculate the mean effect size. We estimated study heterogeneity by employing tau2 and I2 indices and conducting Cochran's Q test. Results The results showed that DBS treatment resulted in a significant improvement in the clinical SUD scales of patients, with an average improvement of 59.6%. The observed relapse rate was 8%. The meta-analysis estimated a mean effect size of 55.9 [40.4; 71.4]. Heterogeneity analysis showed a large degree of heterogeneity among the included studies. Subgroup and meta-regression analysis based on age and SUD type suggested that DBS may be more effective for patients above 45 years of age, and for alcohol and opioid addiction compared to nicotine addiction. Conclusion The current literature suggests that DBS has a moderate effect on SUD symptoms. However, the limited number of studies and small sample size indicate that more research is needed to better understand the factors that influence its effectiveness.
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Affiliation(s)
- Nour Shaheen
- Alexandria Faculty of Medicine, Alexandria, Egypt
| | | | - Can Sarica
- Division of Neurosurgery, University of Toronto, Toronto, ON, Canada
| | - Arun Singh
- Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United States
| | - Mario Zanaty
- Department of Neurological Surgery, Thomas Jefferson University Hospitals, Philadelphia, PA, United States
| | - Karim Johari
- Department of Communication Sciences and Disorders, Louisiana State University, Baton Rouge, LA, United States
| | - Andrew Yang
- Division of Neurosurgery, University of Toronto, Toronto, ON, Canada
| | - Theresa Zesiewicz
- Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL, United States
| | - Brian Dalm
- Department of Neurological Surgery, Ohio State University, Columbus, OH, United States
| | - Yarema Bezchlibnyk
- Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL, United States
| | - Andres M. Lozano
- Division of Neurosurgery, University of Toronto, Toronto, ON, Canada
| | - Oliver Flouty
- Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL, United States
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21
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Fanty L, Yu J, Chen N, Fletcher D, Hey G, Okun M, Wong J. The current state, challenges, and future directions of deep brain stimulation for obsessive compulsive disorder. Expert Rev Med Devices 2023; 20:829-842. [PMID: 37642374 DOI: 10.1080/17434440.2023.2252732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 07/27/2023] [Accepted: 08/24/2023] [Indexed: 08/31/2023]
Abstract
INTRODUCTION Obsessive-compulsive disorder (OCD) is clinically and pathologically heterogenous, with symptoms often refractory to first-line treatments. Deep brain stimulation (DBS) for the treatment of refractory OCD provides an opportunity to adjust and individualize neuromodulation targeting aberrant circuitry underlying OCD. The tailoring of DBS therapy may allow precision in symptom control based on patient-specific pathology. Progress has been made in understanding the potential targets for DBS intervention; however, a consensus on an optimal target has not been agreed upon. AREAS COVERED A literature review of DBS for OCD was performed by querying the PubMed database. The following topics were covered: the evolution of DBS targeting in OCD, the concept of an underlying unified connectomic network, current DBS targets, challenges facing the field, and future directions which could advance personalized DBS in this challenging population. EXPERT OPINION To continue the increasing efficacy of DBS for OCD, we must further explore the optimal DBS response across clinical profiles and neuropsychiatric domains of OCD as well as how interventions targeting multiple points in an aberrant circuit, multiple aberrant circuits, or a connectivity hub impact clinical response. Additionally, biomarkers would be invaluable in programming adjustments and creating a closed-loop paradigm to address symptom fluctuation in daily life.
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Affiliation(s)
- Lauren Fanty
- Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, FL, USA
| | - Jun Yu
- Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, FL, USA
| | - Nita Chen
- Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, FL, USA
| | - Drew Fletcher
- College of Medicine, University of Florida Health Science Center, Gainesville, FL, USA
| | - Grace Hey
- Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, FL, USA
- College of Medicine, University of Florida Health Science Center, Gainesville, FL, USA
| | - Michael Okun
- Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, FL, USA
| | - Josh Wong
- Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, FL, USA
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22
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Beydler E, Katzell L, Putinta K, Holbert R, Carr B. Deep brain stimulation programming for intractable obsessive-compulsive disorder using a long pulse width. Front Psychiatry 2023; 14:1142677. [PMID: 37457764 PMCID: PMC10344357 DOI: 10.3389/fpsyt.2023.1142677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Accepted: 06/14/2023] [Indexed: 07/18/2023] Open
Abstract
Introduction Around 25% of patients with obsessive-compulsive disorder (OCD) do not respond to medication or psychotherapy, producing significant impairment and treatment challenges. Deep Brain Stimulation (DBS) has been shown in multiple blinded trials to be a safe and durable emerging option for treatment-refractory OCD. Intraoperative device interrogation offers a theoretical anchor for starting outpatient DBS programming; however, no definitive post-operative programming algorithm for psychiatrists exists currently. Case Here we present a 58-year-old female with childhood-onset, severe, intractable OCD with multiple failed trials of psychotherapy, medication, and electroconvulsive therapy. After interdisciplinary evaluation, she underwent bilateral electrode implantation targeting the anterior limb of the internal capsule, nucleus accumbens (ALIC/NAc). Intraoperative interrogation afforded sparse information about a preferred lead contact or current density target. Subsequent outpatient interrogation consisted of systematic and independent mapping using monopolar cathodic stimulation with constant current. Modulating bipolar and triple monopolar configurations, amplitude, and pulse width all failed to induce observable effects. Given negligible interrogation feedback, we created an electrical field through the ALIC bilaterally, using the three most ventral contacts to create triple monopoles, with a long pulse width and moderate amperage. Conclusion Three months post-programming, the patient reported significant improvement in OCD symptoms, particularly checking behaviors, with response sustained over the next several months. As with our case, the majority of DBS lead contacts do not induce affective or physiological markers in patients, complicating programming optimization. Here, we discuss an approach to titrating various stimulation parameters and purported mechanisms of physiological markers in DBS for OCD.
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Affiliation(s)
- Emily Beydler
- College of Medicine, University of Florida, Gainesville, FL, United States
| | - Lauren Katzell
- College of Medicine, University of Florida, Gainesville, FL, United States
| | - Kevin Putinta
- Department of Psychiatry, University of South Alabama, Mobile, AL, United States
| | - Richard Holbert
- Department of Psychiatry, University of Florida, Gainesville, FL, United States
| | - Brent Carr
- Department of Psychiatry, University of Florida, Gainesville, FL, United States
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23
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Vega-Zelaya L, Pastor J. The Network Systems Underlying Emotions: The Rational Foundation of Deep Brain Stimulation Psychosurgery. Brain Sci 2023; 13:943. [PMID: 37371421 PMCID: PMC10296681 DOI: 10.3390/brainsci13060943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 06/08/2023] [Accepted: 06/09/2023] [Indexed: 06/29/2023] Open
Abstract
Science and philosophy have tried to understand the origin of emotions for centuries. However, only in the last 150 years have we started to try to understand them in a neuroscientific scope. Emotions include physiological changes involving different systems, such as the endocrine or the musculoskeletal, but they also cause a conscious experience of those changes that are embedded in memory. In addition to the cortico-striato-thalamo-cortical circuit, which is the most important of the basal ganglia, the limbic system and prefrontal circuit are primarily involved in the process of emotion perceptions, thoughts, and memories. The purpose of this review is to describe the anatomy and physiology of the different brain structures involved in circuits that underlie emotions and behaviour, underlying the symptoms of certain psychiatric pathologies. These circuits are targeted during deep brain stimulation (DBS) and knowledge of them is mandatory to understand the clinical-physiological implications for the treatment. We summarize the main outcomes of DBS treatment in several psychiatric illness such as obsessive compulsive disorder, refractory depression, erethism and other conditions, aiming to understand the rationale for selecting these neural systems as targets for DBS.
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Affiliation(s)
| | - Jesús Pastor
- Clinical Neurophysiology, Instituto de Investigación Biomédica Hospital, Universitario de La Princesa, C/Diego de León 62, 28006 Madrid, Spain;
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24
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Acevedo N, J Castle D, Bosanac P, Groves C, L Rossell S. Patient feedback and psychosocial outcomes of deep brain stimulation in people with obsessive-compulsive disorder. J Clin Neurosci 2023; 112:80-85. [PMID: 37119742 DOI: 10.1016/j.jocn.2023.04.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 03/30/2023] [Accepted: 04/18/2023] [Indexed: 05/01/2023]
Abstract
Severe and refractory psychiatric patients can experience complex and profound changes in symptomology, functioning and well-being from deep brain stimulation (DBS) therapy. Currently, the efficacy of DBS is assessed by clinician rated scales of primary symptoms, yet this does not capture the multitude of DBS mediated changes or represent the patient perspective. We aimed to elucidate the patient perspective in psychiatric DBS application by investigating 1) symptomatic, and 2) psychosocial changes, 3) therapeutic expectations and satisfaction, 4) decision-making capacity, and 5) clinical care recommendations from treatment refractory obsessive-compulsive disorder (OCD) DBS patients. Participants enrolled in an open label clinical trial of DBS therapy for OCD who had reached clinical response were invited to participate in a follow up survey. Participants completed a 1) feedback survey relating to goals, expectations, and satisfaction of therapy, and 2) self-report questionnaires on psychosocial functioning including quality of life, cognitive insight, locus of control, rumination, cognitive flexibility, impulsivity, affect, and well-being. Greatest change was reported for quality of life, rumination, affect and cognitive flexibility. Participants reported realistic expectations, high satisfaction, adequate pre-operative education and decision-making capacity; and advocated for greater access to DBS care and more widespread support services. This is the first identified investigation on psychiatric patient perspectives of functioning and therapeutic outcomes following DBS. Insights from the study have implications for informing psychoeducation, clinical practices, and neuroethical debates. We encourage a greater patient-centred and biopsychosocial approach in evaluating and managing OCD DBS patients, by considering personally meaningful goals and addressing symptomatic and psychosocial recovery.
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Affiliation(s)
- Nicola Acevedo
- Centre for Mental Health, Swinburne University of Technology, John Street, Melbourne, VIC, Australia; St Vincent's Hospital, 41 Victoria Parade, Melbourne, VIC, Australia.
| | - David J Castle
- St Vincent's Hospital, 41 Victoria Parade, Melbourne, VIC, Australia; Centre for Addiction and Mental Health, University of Toronto, 27 King's College Cir, Toronto, Canada
| | - Peter Bosanac
- St Vincent's Hospital, 41 Victoria Parade, Melbourne, VIC, Australia; Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia
| | - Clare Groves
- Clarity Health, 55 Nicholson Street, Melbourne, VIC, Australia
| | - Susan L Rossell
- Centre for Mental Health, Swinburne University of Technology, John Street, Melbourne, VIC, Australia; St Vincent's Hospital, 41 Victoria Parade, Melbourne, VIC, Australia
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25
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Malik JA, Agrewala JN. Future perspectives of emerging novel drug targets and immunotherapies to control drug addiction. Int Immunopharmacol 2023; 119:110210. [PMID: 37099943 DOI: 10.1016/j.intimp.2023.110210] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 04/14/2023] [Accepted: 04/15/2023] [Indexed: 04/28/2023]
Abstract
Substance Use Disorder (SUD) is one of the major mental illnesses that is terrifically intensifying worldwide. It is becoming overwhelming due to limited options for treatment. The complexity of addiction disorders is the main impediment to understanding the pathophysiology of the illness. Hence, unveiling the complexity of the brain through basic research, identification of novel signaling pathways, the discovery of new drug targets, and advancement in cutting-edge technologies will help control this disorder. Additionally, there is a great hope of controlling the SUDs through immunotherapeutic measures like therapeutic antibodies and vaccines. Vaccines have played a cardinal role in eliminating many diseases like polio, measles, and smallpox. Further, vaccines have controlled many diseases like cholera, dengue, diphtheria, Haemophilus influenza type b (Hib), human papillomavirus, influenza, Japanese encephalitis, etc. Recently, COVID-19 was controlled in many countries by vaccination. Currently, continuous effort is done to develop vaccines against nicotine, cocaine, morphine, methamphetamine, and heroin. Antibody therapy against SUDs is another important area where serious attention is required. Antibodies have contributed substantially against many serious diseases like diphtheria, rabies, Crohn's disease, asthma, rheumatoid arthritis, and bladder cancer. Antibody therapy is gaining immense momentum due to its success rate in cancer treatment. Furthermore, enormous advancement has been made in antibody therapy due to the generation of high-efficiency humanized antibodies with a long half-life. The advantage of antibody therapy is its instant outcome. This article's main highlight is discussing the drug targets of SUDs and their associated mechanisms. Importantly, we have also discussed the scope of prophylactic measures to eliminate drug dependence.
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Affiliation(s)
- Jonaid Ahmad Malik
- Immunology laboratory, Indian Institute of Technology Ropar, Rupnagar, Punjab, India
| | - Javed N Agrewala
- Immunology laboratory, Indian Institute of Technology Ropar, Rupnagar, Punjab, India.
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26
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Saez I, Gu X. Invasive Computational Psychiatry. Biol Psychiatry 2023; 93:661-670. [PMID: 36641365 PMCID: PMC10038930 DOI: 10.1016/j.biopsych.2022.09.032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 08/25/2022] [Accepted: 09/27/2022] [Indexed: 01/16/2023]
Abstract
Computational psychiatry, a relatively new yet prolific field that aims to understand psychiatric disorders with formal theories about the brain, has seen tremendous growth in the past decade. Despite initial excitement, actual progress made by computational psychiatry seems stagnant. Meanwhile, understanding of the human brain has benefited tremendously from recent progress in intracranial neuroscience. Specifically, invasive techniques such as stereotactic electroencephalography, electrocorticography, and deep brain stimulation have provided a unique opportunity to precisely measure and causally modulate neurophysiological activity in the living human brain. In this review, we summarize progress and drawbacks in both computational psychiatry and invasive electrophysiology and propose that their combination presents a highly promising new direction-invasive computational psychiatry. The value of this approach is at least twofold. First, it advances our mechanistic understanding of the neural computations of mental states by providing a spatiotemporally precise depiction of neural activity that is traditionally unattainable using noninvasive techniques with human subjects. Second, it offers a direct and immediate way to modulate brain states through stimulation of algorithmically defined neural regions and circuits (i.e., algorithmic targeting), thus providing both causal and therapeutic insights. We then present depression as a use case where the combination of computational and invasive approaches has already shown initial success. We conclude by outlining future directions as a road map for this exciting new field as well as presenting cautions about issues such as ethical concerns and generalizability of findings.
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Affiliation(s)
- Ignacio Saez
- Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.
| | - Xiaosi Gu
- Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.
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27
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Halgren AS, Siegel Z, Golden R, Bazhenov M. Multielectrode Cortical Stimulation Selectively Induces Unidirectional Wave Propagation of Excitatory Neuronal Activity in Biophysical Neural Model. J Neurosci 2023; 43:2482-2496. [PMID: 36849415 PMCID: PMC10082457 DOI: 10.1523/jneurosci.1784-21.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 12/27/2022] [Accepted: 01/13/2023] [Indexed: 03/01/2023] Open
Abstract
Cortical stimulation is emerging as an experimental tool in basic research and a promising therapy for a range of neuropsychiatric conditions. As multielectrode arrays enter clinical practice, the possibility of using spatiotemporal patterns of electrical stimulation to induce desired physiological patterns has become theoretically possible, but in practice can only be implemented by trial-and-error because of a lack of predictive models. Experimental evidence increasingly establishes traveling waves as fundamental to cortical information-processing, but we lack an understanding of how to control wave properties despite rapidly improving technologies. This study uses a hybrid biophysical-anatomical and neural-computational model to predict and understand how a simple pattern of cortical surface stimulation could induce directional traveling waves via asymmetric activation of inhibitory interneurons. We found that pyramidal cells and basket cells are highly activated by the anodal electrode and minimally activated by the cathodal electrodes, while Martinotti cells are moderately activated by both electrodes but exhibit a slight preference for cathodal stimulation. Network model simulations found that this asymmetrical activation results in a traveling wave in superficial excitatory cells that propagates unidirectionally away from the electrode array. Our study reveals how asymmetric electrical stimulation can easily facilitate traveling waves by relying on two distinct types of inhibitory interneuron activity to shape and sustain the spatiotemporal dynamics of endogenous local circuit mechanisms.SIGNIFICANCE STATEMENT Electrical brain stimulation is becoming increasingly useful to probe the workings of brain and to treat a variety of neuropsychiatric disorders. However, stimulation is currently performed in a trial-and-error fashion as there are no methods to predict how different electrode arrangements and stimulation paradigms will affect brain functioning. In this study, we demonstrate a hybrid modeling approach, which makes experimentally testable predictions that bridge the gap between the microscale effects of multielectrode stimulation and the resultant circuit dynamics at the mesoscale. Our results show how custom stimulation paradigms can induce predictable, persistent changes in brain activity, which has the potential to restore normal brain function and become a powerful therapy for neurological and psychiatric conditions.
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Affiliation(s)
- Alma S Halgren
- Department of Medicine, University of California - San Diego, La Jolla, California 92093-7374
- Department of Integrative Biology, University of California - Berkeley, Berkeley, California 94720
| | - Zarek Siegel
- Department of Medicine, University of California - San Diego, La Jolla, California 92093-7374
- Neurosciences Graduate Program, University of California - San Diego, La Jolla, California 92093-7374
| | - Ryan Golden
- Department of Medicine, University of California - San Diego, La Jolla, California 92093-7374
- Neurosciences Graduate Program, University of California - San Diego, La Jolla, California 92093-7374
| | - Maxim Bazhenov
- Department of Medicine, University of California - San Diego, La Jolla, California 92093-7374
- Neurosciences Graduate Program, University of California - San Diego, La Jolla, California 92093-7374
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28
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Alarie ME, Provenza NR, Avendano-Ortega M, McKay SA, Waite AS, Mathura RK, Herron JA, Sheth SA, Borton DA, Goodman WK. Artifact characterization and mitigation techniques during concurrent sensing and stimulation using bidirectional deep brain stimulation platforms. Front Hum Neurosci 2022; 16:1016379. [PMID: 36337849 PMCID: PMC9626519 DOI: 10.3389/fnhum.2022.1016379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 10/03/2022] [Indexed: 11/30/2022] Open
Abstract
Bidirectional deep brain stimulation (DBS) platforms have enabled a surge in hours of recordings in naturalistic environments, allowing further insight into neurological and psychiatric disease states. However, high amplitude, high frequency stimulation generates artifacts that contaminate neural signals and hinder our ability to interpret the data. This is especially true in psychiatric disorders, for which high amplitude stimulation is commonly applied to deep brain structures where the native neural activity is miniscule in comparison. Here, we characterized artifact sources in recordings from a bidirectional DBS platform, the Medtronic Summit RC + S, with the goal of optimizing recording configurations to improve signal to noise ratio (SNR). Data were collected from three subjects in a clinical trial of DBS for obsessive-compulsive disorder. Stimulation was provided bilaterally to the ventral capsule/ventral striatum (VC/VS) using two independent implantable neurostimulators. We first manipulated DBS amplitude within safe limits (2–5.3 mA) to characterize the impact of stimulation artifacts on neural recordings. We found that high amplitude stimulation produces slew overflow, defined as exceeding the rate of change that the analog to digital converter can accurately measure. Overflow led to expanded spectral distortion of the stimulation artifact, with a six fold increase in the bandwidth of the 150.6 Hz stimulation artifact from 147–153 to 140–180 Hz. By increasing sense blank values during high amplitude stimulation, we reduced overflow by as much as 30% and improved artifact distortion, reducing the bandwidth from 140–180 Hz artifact to 147–153 Hz. We also identified artifacts that shifted in frequency through modulation of telemetry parameters. We found that telemetry ratio changes led to predictable shifts in the center-frequencies of the associated artifacts, allowing us to proactively shift the artifacts outside of our frequency range of interest. Overall, the artifact characterization methods and results described here enable increased data interpretability and unconstrained biomarker exploration using data collected from bidirectional DBS devices.
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Affiliation(s)
| | - Nicole R. Provenza
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
| | - Michelle Avendano-Ortega
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, United States
| | - Sarah A. McKay
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, United States
| | - Ayan S. Waite
- Brown University School of Engineering, Providence, RI, United States
| | - Raissa K. Mathura
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
| | - Jeffrey A. Herron
- Department of Neurological Surgery, University of Washington, Seattle, WA, United States
| | - Sameer A. Sheth
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
| | - David A. Borton
- Brown University School of Engineering, Providence, RI, United States
- Department of Veterans Affairs, Center for Neurorestoration and Neurotechnology, Rehabilitation R&D Service, Providence, RI, United States
| | - Wayne K. Goodman
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, United States
- *Correspondence: Wayne K. Goodman,
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29
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Gadot R, Najera R, Hirani S, Anand A, Storch E, Goodman WK, Shofty B, Sheth SA. Efficacy of deep brain stimulation for treatment-resistant obsessive-compulsive disorder: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2022; 93:jnnp-2021-328738. [PMID: 36127157 DOI: 10.1136/jnnp-2021-328738] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Accepted: 05/22/2022] [Indexed: 11/03/2022]
Abstract
Deep brain stimulation (DBS) is an established and growing intervention for treatment-resistant obsessive-compulsive disorder (TROCD). We assessed current evidence on the efficacy of DBS in alleviating OCD and comorbid depressive symptoms including newly available evidence from recent trials and a deeper risk of bias analysis than previously available. PubMed and EMBASE databases were systematically queried using Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. We included studies reporting primary data on multiple patients who received DBS therapy with outcomes reported through the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Primary effect measures included Y-BOCS mean difference and per cent reduction as well as responder rate (≥35% Y-BOCS reduction) at last follow-up. Secondary effect measures included standardised depression scale reduction. Risk of bias assessments were performed on randomised controlled (RCTs) and non-randomised trials. Thirty-four studies from 2005 to 2021, 9 RCTs (n=97) and 25 non-RCTs (n=255), were included in systematic review and meta-analysis based on available outcome data. A random-effects model indicated a meta-analytical average 14.3 point or 47% reduction (p<0.01) in Y-BOCS scores without significant difference between RCTs and non-RCTs. At last follow-up, 66% of patients were full responders to DBS therapy. Sensitivity analyses indicated a low likelihood of small study effect bias in reported outcomes. Secondary analysis revealed a 1 standardised effect size (Hedges' g) reduction in depressive scale symptoms. Both RCTs and non-RCTs were determined to have a predominantly low risk of bias. A strong evidence base supports DBS for TROCD in relieving both OCD and comorbid depression symptoms in appropriately selected patients.
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Affiliation(s)
- Ron Gadot
- Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA
| | - Ricardo Najera
- Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA
| | - Samad Hirani
- Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA
| | - Adrish Anand
- Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA
| | - Eric Storch
- Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas, USA
| | - Wayne K Goodman
- Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas, USA
| | - Ben Shofty
- Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA
| | - Sameer A Sheth
- Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA
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30
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Porwal MH, Karra H, Sharma U, Bhatti D. Deep brain stimulation for refractory obsessive-compulsive disorder: A review and analysis of the FDA MAUDE database. Surg Neurol Int 2022; 13:399. [PMID: 36128133 PMCID: PMC9479641 DOI: 10.25259/sni_613_2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Accepted: 08/18/2022] [Indexed: 11/17/2022] Open
Abstract
Background: Deep brain stimulation (DBS) is used as a treatment option for patients diagnosed with a form of obsessive-compulsive disorder (OCD) that is highly resistant to conventional treatment methods. In 2009, DBS was granted a humanitarian device exemption-approval by the Food and Drug Administration after promising preliminary data. Monitoring of long-term safety data through post market surveillance of adverse events has not yet been conducted for DBS in OCD patients. This study aims to address this critical knowledge gap. Methods: All patient- and device-related (PR; DR) reports from January 1, 2012, to December 31, 2021, were downloaded and compiled from the manufacturer and user facility device experience (MAUDE) database pertaining to DBS for OCD using the product class name “Deep Brain Stimulator For OCD.” Data in this study were examined using descriptive statistics to evaluate for frequency of reporting. Results: The most frequently reported PR adverse event categories included psychiatric (40%), neurological (19%), other (14%), decreased therapeutic response (10%), and infections (10%). The most frequent DR reports were high impedance (14%), energy output problem (7%), battery problem (7%), malposition of device (7%), and improper/incorrect procedure or method (7%). Conclusion: The PR and DR adverse events in our study align with the previous findings of adverse events. They also further solidify that DBS for refractory OCD may be a viable option for the right patient population. However, further studies are essential given the limitations of the MAUDE database.
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Affiliation(s)
- Mokshal H. Porwal
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin,
| | - Hamsitha Karra
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin,
| | - Umesh Sharma
- Department of Neurology, Orlando Regional Medical Center,
| | - Danish Bhatti
- Department of Neurology, University of Central Florida College of Medicine, Orlando, Florida, United States
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31
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Yuen J, Kouzani AZ, Berk M, Tye SJ, Rusheen AE, Blaha CD, Bennet KE, Lee KH, Shin H, Kim JH, Oh Y. Deep Brain Stimulation for Addictive Disorders-Where Are We Now? Neurotherapeutics 2022; 19:1193-1215. [PMID: 35411483 PMCID: PMC9587163 DOI: 10.1007/s13311-022-01229-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/18/2022] [Indexed: 10/18/2022] Open
Abstract
In the face of a global epidemic of drug addiction, neglecting to develop new effective therapies will perpetuate the staggering human and economic costs of substance use. This review aims to summarize and evaluate the preclinical and clinical studies of deep brain stimulation (DBS) as a novel therapy for refractory addiction, in hopes to engage and inform future research in this promising novel treatment avenue. An electronic database search (MEDLINE, EMBASE, Cochrane library) was performed using keywords and predefined inclusion criteria between 1974 and 6/18/2021 (registered on Open Science Registry). Selected articles were reviewed in full text and key details were summarized and analyzed to understand DBS' therapeutic potential and possible mechanisms of action. The search yielded 25 animal and 22 human studies. Animal studies showed that DBS of targets such as nucleus accumbens (NAc), insula, and subthalamic nucleus reduces drug use and seeking. All human studies were case series/reports (level 4/5 evidence), mostly targeting the NAc with generally positive outcomes. From the limited evidence in the literature, DBS, particularly of the NAc, appears to be a reasonable last resort option for refractory addictive disorders. We propose that future research in objective electrophysiological (e.g., local field potentials) and neurochemical (e.g., extracellular dopamine levels) biomarkers would assist monitoring the progress of treatment and developing a closed-loop DBS system. Preclinical literature also highlighted the prefrontal cortex as a promising DBS target, which should be explored in human research.
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Affiliation(s)
- Jason Yuen
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, 55905, USA
- Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong VIC 3216, Australia
| | - Abbas Z Kouzani
- School of Engineering, Deakin University, Geelong VIC 3216, Australia
| | - Michael Berk
- Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong VIC 3216, Australia
| | - Susannah J Tye
- Queensland Brain Institute, The University of Queensland, St Lucia, QLD, 4072, Australia
- Department of Psychiatry & Psychology, Mayo Clinic, Rochester, MN, 55905, USA
- Department of Psychiatry, University of Minnesota, Minneapolis, MN, 55455, USA
- Department of Psychiatry, Emory University, Atlanta, GA, 30322, USA
| | - Aaron E Rusheen
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, 55905, USA
| | - Charles D Blaha
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, 55905, USA
| | - Kevin E Bennet
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, 55905, USA
- Division of Engineering, Mayo Clinic, Rochester, MN, 55905, USA
| | - Kendall H Lee
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, 55905, USA
- Department of Biomedical Engineering, Mayo Clinic, Rochester, MN, 55905, USA
| | - Hojin Shin
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, 55905, USA
| | - Jee Hyun Kim
- Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong VIC 3216, Australia.
| | - Yoonbae Oh
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, 55905, USA.
- Department of Biomedical Engineering, Mayo Clinic, Rochester, MN, 55905, USA.
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32
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Mosley PE, Velakoulis D, Farrand S, Marsh R, Mohan A, Castle D, Sachdev PS. Deep brain stimulation for treatment-refractory obsessive-compulsive disorder should be an accepted therapy in Australia. Aust N Z J Psychiatry 2022; 56:430-436. [PMID: 34263654 DOI: 10.1177/00048674211031482] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Deep brain stimulation has shown promise for the treatment of severe, treatment-refractory obsessive-compulsive disorder. With the recent publication of the first Australian, randomised, sham-controlled trial of deep brain stimulation for obsessive-compulsive disorder, there are now four placebo-controlled trials demonstrating the efficacy of this therapy. Together with recent data identifying a biological substrate of effective stimulation that can predict response and that has been successfully reproduced, studies comparing and finding equivalent efficacy among different targets, as well as recent, large, open trials supporting the long-term effectiveness of deep brain stimulation, we argue that this should now be considered an accepted therapy for a select group of patients in the Australasian setting. We call on the Royal Australian and New Zealand College of Psychiatrists to revise their memorandum describing deep brain stimulation for obsessive-compulsive disorder as an 'experimental' treatment and recognise that it has proven efficacy. We stress that this should remain a therapy offered only to those with high treatment-refractory illnesses and only at specialised centres where there is an experienced multidisciplinary team involved in work-up, implantation and follow-up and also where frameworks are in place to provide careful clinical governance and ensure appropriate fully informed consent.
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Affiliation(s)
- Philip E Mosley
- Clinical Brain Networks Group, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.,Neurosciences Queensland, St Andrew's War Memorial Hospital, Spring Hill, QLD, Australia.,Queensland Brain Institute, The University of Queensland, St Lucia, QLD, Australia.,Faculty of Medicine, The University of Queensland, Herston, QLD, Australia.,Biomedical Informatics Group, CSIRO, Herston, QLD, Australia
| | - Dennis Velakoulis
- Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia.,Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Parkville, VIC, Australia
| | - Sarah Farrand
- Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia.,Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Parkville, VIC, Australia
| | - Rodney Marsh
- Neurosciences Queensland, St Andrew's War Memorial Hospital, Spring Hill, QLD, Australia.,Faculty of Medicine, The University of Queensland, Herston, QLD, Australia
| | - Adith Mohan
- Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.,Neuropsychiatric Institute, The Prince of Wales Hospital, Randwick, NSW, Australia
| | - David Castle
- Centre for Complex Interventions, Centre for Addiction and Mental Health, Toronto, ON, Canada.,Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Perminder S Sachdev
- Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.,Neuropsychiatric Institute, The Prince of Wales Hospital, Randwick, NSW, Australia
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33
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Luber B, Davis SW, Deng ZD, Murphy D, Martella A, Peterchev AV, Lisanby SH. Using diffusion tensor imaging to effectively target TMS to deep brain structures. Neuroimage 2022; 249:118863. [PMID: 34974116 PMCID: PMC8851689 DOI: 10.1016/j.neuroimage.2021.118863] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Revised: 09/08/2021] [Accepted: 12/23/2021] [Indexed: 10/19/2022] Open
Abstract
TMS has become a powerful tool to explore cortical function, and in parallel has proven promising in the development of therapies for various psychiatric and neurological disorders. Unfortunately, much of the inference of the direct effects of TMS has been assumed to be limited to the area a few centimeters beneath the scalp, though clearly more distant regions are likely to be influenced by structurally connected stimulation sites. In this study, we sought to develop a novel paradigm to individualize TMS coil placement to non-invasively achieve activation of specific deep brain targets of relevance to the treatment of psychiatric disorders. In ten subjects, structural diffusion imaging tractography data were used to identify an accessible cortical target in the right frontal pole that demonstrated both anatomic and functional connectivity to right Brodmann area 25 (BA25). Concurrent TMS-fMRI interleaving was used with a series of single, interleaved TMS pulses applied to the right frontal pole at four intensity levels ranging from 80% to 140% of motor threshold. In nine of ten subjects, TMS to the individualized frontal pole sites resulted in significant linear increase in BOLD activation of BA25 with increasing TMS intensity. The reliable activation of BA25 in a dosage-dependent manner suggests the possibility that the careful combination of imaging with TMS can make use of network properties to help overcome depth limitations and allow noninvasive brain stimulation to influence deep brain structures.
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Affiliation(s)
- Bruce Luber
- Noninvasive Neuromodulation Unit, Experimental Therapeutics & Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States.
| | - Simon W Davis
- Department of Neurology, Duke University School of Medicine, Durham, NC, United States
| | - Zhi-De Deng
- Noninvasive Neuromodulation Unit, Experimental Therapeutics & Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States; Department of Psychiatry & Behavioral Sciences, Duke University School of Medicine, Durham, NC, United States
| | - David Murphy
- Department of Psychiatry & Behavioral Sciences, Duke University School of Medicine, Durham, NC, United States
| | - Andrew Martella
- Department of Psychiatry & Behavioral Sciences, Duke University School of Medicine, Durham, NC, United States
| | - Angel V Peterchev
- Department of Psychiatry & Behavioral Sciences, Duke University School of Medicine, Durham, NC, United States; Department of Biomedical Engineering, Duke University, Durham, NC, United States; Department of Electrical and Computer Engineering, Duke University, Durham, NC, United States; Department of Neurosurgery, Duke University School of Medicine, Durham, NC, United States
| | - Sarah H Lisanby
- Noninvasive Neuromodulation Unit, Experimental Therapeutics & Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States; Department of Psychiatry & Behavioral Sciences, Duke University School of Medicine, Durham, NC, United States
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34
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Corripio I, Roldán A, McKenna P, Sarró S, Alonso-Solís A, Salgado L, Álvarez E, Molet J, Pomarol-Clotet E, Portella M. Target selection for deep brain stimulation in treatment resistant schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2022; 112:110436. [PMID: 34517055 DOI: 10.1016/j.pnpbp.2021.110436] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 08/28/2021] [Accepted: 09/07/2021] [Indexed: 11/19/2022]
Abstract
The use of deep brain stimulation (DBS) in treatment resistant patients with schizophrenia is of considerable current interest, but where to site the electrodes is challenging. This article reviews rationales for electrode placement in schizophrenia based on evidence for localized brain abnormality in the disorder and the targets that have been proposed and employed to date. The nucleus accumbens and the subgenual anterior cingulate cortex are of interest on the grounds that they are sites of potential pathologically increased brain activity in schizophrenia and so susceptible to the local inhibitory effects of DBS; both sites have been employed in trials of DBS in schizophrenia. Based on other lines of reasoning, the ventral tegmental area, the substantia nigra pars reticulata and the habenula have also been proposed and in some cases employed. The dorsolateral prefrontal cortex has not been suggested, probably reflecting evidence that it is underactive rather than overactive in schizophrenia. The hippocampus is also of theoretical interest but there is no clear functional imaging evidence that it shows overactivity in schizophrenia. On current evidence, the nucleus accumbens may represent the strongest candidate for DBS electrode placement in schizophrenia, with the substantia nigra pars reticulata also showing promise in a single case report; the ventral tegmental area is also of potential interest, though it remains untried.
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Affiliation(s)
- Iluminada Corripio
- Psychiatry Department, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
| | - Alexandra Roldán
- Psychiatry Department, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
| | - Peter McKenna
- FIDMAG Germanes Hospitalàries, Sant Boi de Llobregat, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
| | - Salvador Sarró
- FIDMAG Germanes Hospitalàries, Sant Boi de Llobregat, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
| | - Anna Alonso-Solís
- Psychiatry Department, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
| | - Laura Salgado
- Neurosurgery Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain
| | - Enric Álvarez
- Psychiatry Department, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
| | - Joan Molet
- Neurosurgery Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain
| | - Edith Pomarol-Clotet
- FIDMAG Germanes Hospitalàries, Sant Boi de Llobregat, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
| | - Maria Portella
- Psychiatry Department, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
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35
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Murray SB, Strober M, Tadayonnejad R, Bari AA, Feusner JD. Neurosurgery and neuromodulation for anorexia nervosa in the 21st century: a systematic review of treatment outcomes. Eat Disord 2022; 30:26-53. [PMID: 32991247 PMCID: PMC8386186 DOI: 10.1080/10640266.2020.1790270] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
As current psychosocial and pharmacological interventions show limited efficacy in the treatment of anorexia nervosa (AN), interest in the potential value of neurosurgical intervention and neuromodulation in managing severe and enduring illness has grown. We conducted a systematic review of 20 trials of neurosurgical and neuromodulatory treatments for AN, including neurosurgical ablation, deep brain stimulation (DBS), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS). Overall, there is evidence to support the role of stereotactic ablation and DBS in the treatment of AN. In contrast, results for rTMS and tDCS have been modest and generally more mixed. Neurosurgical treatment may offer important new avenues for the treatment of AN. Additional randomized clinical trials with comparable patient populations will be needed, in which change in affective, cognitive, and perceptual symptom phenomena, and interrogation of targeted circuits, pre- and post-intervention, are carefully documented.
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Affiliation(s)
- Stuart B Murray
- Department of Psychiatry and the Behavioral Sciences, University of Southern California, Los Angeles, California, USA
| | - Michael Strober
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA
| | - Reza Tadayonnejad
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA
| | - Ausaf A Bari
- Department of Neurosurgery, University of California, Los Angeles, Los Angeles, CA, USA
| | - Jamie D Feusner
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA
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Kuhn T, Haroon J, Spivak NM. A Systematic Approach to Neuropsychiatric Intervention: Functional Neuroanatomy Underlying Symptom Domains as Targets for Treatment. FOCUS (AMERICAN PSYCHIATRIC PUBLISHING) 2022; 20:45-54. [PMID: 35746937 PMCID: PMC9063598 DOI: 10.1176/appi.focus.20210024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
An ever-growing population experiences a wide range of psychopathologies, and there is now more than ever a need for clear differential diagnoses between disorders. Furthering this need is the fact that many psychological, psychiatric, and neurological disorders have overlapping features. Functional neuroimaging has been shown to differentiate not only between the function of different brain structures but also between the roles of these structures in functional networks. The aim of this article is to aid in the goal of parsing out disorders on the basis of specific symptom domains by utilizing the most recent literature on functional networks. Current literature on the role of brain networks in relation to different psychopathological symptom domains is examined and corresponding circuit-based therapies that have been or may be used to treat them are discussed. Research on depression, obsession and compulsions, addiction, anxiety, and psychosis is reviewed. An understanding of networks and their specific dysfunctions opens the possibility of a new form of psychopathological treatment.
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Affiliation(s)
- Taylor Kuhn
- Department of Psychiatry and Biobehavioral Sciences (all authors) and UCLA-Caltech Medical Scientist Training Program (Spivak), David Geffen School of Medicine, University of California, Los Angeles
| | - Jonathan Haroon
- Department of Psychiatry and Biobehavioral Sciences (all authors) and UCLA-Caltech Medical Scientist Training Program (Spivak), David Geffen School of Medicine, University of California, Los Angeles
| | - Norman M Spivak
- Department of Psychiatry and Biobehavioral Sciences (all authors) and UCLA-Caltech Medical Scientist Training Program (Spivak), David Geffen School of Medicine, University of California, Los Angeles
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37
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Deep brain stimulation of the "medial forebrain bundle": a strategy to modulate the reward system and manage treatment-resistant depression. Mol Psychiatry 2022; 27:574-592. [PMID: 33903731 DOI: 10.1038/s41380-021-01100-6] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 03/21/2021] [Accepted: 04/01/2021] [Indexed: 02/02/2023]
Abstract
The medial forebrain bundle-a white matter pathway projecting from the ventral tegmental area-is a structure that has been under a lot of scrutinies recently due to its implications in the modulation of certain affective disorders such as major depression. In the following, we will discuss major depression in the context of being a disorder dependent on multiple relevant networks, the pathological performance of which is responsible for the manifestation of various symptoms of the disease which extend into emotional, motivational, physiological, and also cognitive domains of daily living. We will focus on the reward system, an evolutionarily conserved pathway whose underperformance leads to anhedonia and lack of motivation, which are key traits in depression. In the field of deep brain stimulation (DBS), different "hypothesis-driven" targets have been chosen as the subject of clinical trials on efficacy in the treatment-resistant depressed patient. The "medial forebrain bundle" is one such target for DBS, and has had remarkably rapid success in alleviating depressive symptoms, improving anhedonia and motivation. We will review what we have learned from pre-clinical animal studies on defining this white matter tract, its connectivity, and the complex molecular (i.e., neurotransmitter) mechanisms by which its modulation exerts its effects. Imaging studies in the form of tractographic depictions have elucidated its presence in the human brain. Such has led to ongoing clinical trials of DBS targeting this pathway to assess efficacy, which is promising yet still lack in sufficient numbers. Ultimately, one must confirm the mechanism of action and validate proof of antidepressant effect in order to have such treatment become mainstream, to promote widespread improvement in the quality of life of suffering patients.
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38
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Ahmari SE, Rauch SL. The prefrontal cortex and OCD. Neuropsychopharmacology 2022; 47:211-224. [PMID: 34400778 PMCID: PMC8617188 DOI: 10.1038/s41386-021-01130-2] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 07/13/2021] [Accepted: 07/22/2021] [Indexed: 01/03/2023]
Abstract
Obsessive Compulsive Disorder (OCD) is a highly prevalent and severe neuropsychiatric disorder, with an incidence of 1.5-3% worldwide. However, despite the clear public health burden of OCD and relatively well-defined symptom criteria, effective treatments are still limited, spotlighting the need for investigation of the neural substrates of the disorder. Human neuroimaging studies have consistently highlighted abnormal activity patterns in prefrontal cortex (PFC) regions and connected circuits in OCD during both symptom provocation and performance of neurocognitive tasks. Because of recent technical advances, these findings can now be leveraged to develop novel targeted interventions. Here we will highlight current theories regarding the role of the prefrontal cortex in the generation of OCD symptoms, discuss ways in which this knowledge can be used to improve treatments for this often disabling illness, and lay out challenges in the field for future study.
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Affiliation(s)
- Susanne E Ahmari
- Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
- Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
- Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, PA, USA.
| | - Scott L Rauch
- Department of Psychiatry, McLean Hospital, Belmont, MA, USA
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA
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39
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Borron BM, Dougherty DD. Deep Brain Stimulation for Intractable Obsessive-Compulsive Disorder and Treatment-Resistant Depression. FOCUS (AMERICAN PSYCHIATRIC PUBLISHING) 2022; 20:55-63. [PMID: 35746939 PMCID: PMC9063589 DOI: 10.1176/appi.focus.20210029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
In deep brain stimulation (DBS), a neurostimulation device is implanted to generate electrical fields in targeted deep brain regions in order to affect circuits associated with neuropsychiatric illness for potential therapeutic benefit. The development of DBS has followed a decades-long history of psychiatric neurosurgery, with advances in pacemakers and spinal neurostimulation devices allowing for the use of DBS in the treatment of neuropsychiatric disorders. Currently, deep brain stimulation for psychiatric illness has been approved by the U.S. Food and Drug Administration for the treatment of intractable obsessive-compulsive disorder, through a Humanitarian Device Exemption. The use of DBS for treatment-resistant depression is another promising application of this technology. Several potential targets of DBS have shown promise for treating neuropsychiatric illness, but few have demonstrated efficacy in randomized controlled trials. Future directions for DBS research will likely include modified trial designs, refined targets, the use of tractography for more specific and individualized targeting, and development of closed-loop DBS.
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40
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Baldermann JC, Schüller T, Kohl S, Voon V, Li N, Hollunder B, Figee M, Haber SN, Sheth SA, Mosley PE, Huys D, Johnson KA, Butson C, Ackermans L, Bouwens van der Vlis T, Leentjens AFG, Barbe M, Visser-Vandewalle V, Kuhn J, Horn A. Connectomic Deep Brain Stimulation for Obsessive-Compulsive Disorder. Biol Psychiatry 2021; 90:678-688. [PMID: 34482949 DOI: 10.1016/j.biopsych.2021.07.010] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 06/29/2021] [Accepted: 07/01/2021] [Indexed: 01/17/2023]
Abstract
Obsessive-compulsive disorder is among the most disabling psychiatric disorders. Although deep brain stimulation is considered an effective treatment, its use in clinical practice is not fully established. This is, at least in part, due to ambiguity about the best suited target and insufficient knowledge about underlying mechanisms. Recent advances suggest that changes in broader brain networks are responsible for improvement of obsessions and compulsions, rather than local impact at the stimulation site. These findings were fueled by innovative methodological approaches using brain connectivity analyses in combination with neuromodulatory interventions. Such a connectomic approach for neuromodulation constitutes an integrative account that aims to characterize optimal target networks. In this critical review, we integrate findings from connectomic studies and deep brain stimulation interventions to characterize a neural network presumably effective in reducing obsessions and compulsions. To this end, we scrutinize methodologies and seemingly conflicting findings with the aim to merge observations to identify common and diverse pathways for treating obsessive-compulsive disorder. Ultimately, we propose a unified network that-when modulated by means of cortical or subcortical interventions-alleviates obsessive-compulsive symptoms.
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Affiliation(s)
- Juan Carlos Baldermann
- Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
| | - Thomas Schüller
- Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Sina Kohl
- Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Valerie Voon
- Department of Psychiatry, Cambridge University, Cambridge, United Kingdom
| | - Ningfei Li
- Department of Neurology, Movement Disorders and Neuromodulation Section, Charité - University Medicine Berlin, Berlin, Germany
| | - Barbara Hollunder
- Department of Neurology, Movement Disorders and Neuromodulation Section, Charité - University Medicine Berlin, Berlin, Germany; Einstein Center for Neurosciences, Charité - University Medicine Berlin, Berlin, Germany; Faculty of Philosophy, Humboldt University of Berlin, Berlin School of Mind and Brain, Berlin, Germany
| | - Martijn Figee
- Department of Psychiatry, Mount Sinai Hospital, New York, New York
| | - Suzanne N Haber
- Department of Pharmacology and Physiology, University of Rochester School of Medicine, Rochester, New York; Basic Neuroscience Division, Harvard Medical School, McLean Hospital, Belmont, Massachusetts
| | - Sameer A Sheth
- Department of Neurosurgery, Baylor College of Medicine, Houston, Texas
| | - Philip E Mosley
- Systems Neuroscience Group, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia; Queensland Brain Institute, University of Queensland, St Lucia, Queensland, Australia
| | - Daniel Huys
- Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Kara A Johnson
- Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida
| | - Christopher Butson
- Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, Utah; Department of Biomedical Engineering, University of Utah, Salt Lake City, Utah
| | - Linda Ackermans
- School of Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands
| | | | - Albert F G Leentjens
- School of Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands
| | - Michael Barbe
- Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Veerle Visser-Vandewalle
- Department of Stereotactic and Functional Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Jens Kuhn
- Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Department of Psychiatry, Psychotherapy and Psychosomatic, Johanniter Hospital Oberhausen, Oberhausen, Germany
| | - Andreas Horn
- Department of Neurology, Movement Disorders and Neuromodulation Section, Charité - University Medicine Berlin, Berlin, Germany
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41
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Graat I, Mocking R, Figee M, Vulink N, de Koning P, Ooms P, Mantione M, van den Munckhof P, Schuurman R, Denys D. Long-term Outcome of Deep Brain Stimulation of the Ventral Part of the Anterior Limb of the Internal Capsule in a Cohort of 50 Patients With Treatment-Refractory Obsessive-Compulsive Disorder. Biol Psychiatry 2021; 90:714-720. [PMID: 33131717 DOI: 10.1016/j.biopsych.2020.08.018] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 08/20/2020] [Accepted: 08/20/2020] [Indexed: 12/23/2022]
Abstract
BACKGROUND Deep brain stimulation (DBS) is an effective intervention for patients with severe treatment-refractory obsessive-compulsive disorder (OCD). Our aim was to examine long-term effectiveness and tolerability of DBS and its impact on functioning and well-being. METHODS Fifty patients with severe treatment-refractory OCD received DBS of the ventral part of the anterior limb of the internal capsule and were followed for at least 3 years following implantation (mean 6.8 ± 3 years). Primary effectiveness was assessed by change in Yale-Brown Obsessive Compulsive Scale scores. Secondary effectiveness measures included Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, World Health Organization Quality of Life Scale-Brief Version, Global Assessment of Functioning, and a scale assessing functioning in work, family, and social life. Adverse effects of DBS were examined with a structured interview (n = 38). RESULTS At long-term follow-up, OCD symptoms decreased by 39% (p < .001), and half of the patients were responders (≥35% decrease of Yale-Brown Obsessive Compulsive Scale score). Anxiety and depressive symptoms decreased significantly, with reductions of 48% and 50%, respectively. The World Health Organization Quality of Life Scale-Brief Version general score improved significantly, as did 3 of 4 subdomains. Both clinician- and patient-rated functioning improved substantially (p < .001). The unemployment rate decreased from 78% at baseline to 58% at last follow-up (z = -1.90, p = .058), and 21 patients stopped or decreased psychotropic medication (z = -2.887, p = .004). Long-term adverse effects included cognitive complaints and fatigue. Serious adverse events included 1 suicide attempt, related to comorbid depression. CONCLUSIONS Our results provide evidence that DBS of the ventral part of the anterior limb of the internal capsule is effective and tolerable for treatment-refractory OCD in the long term and improves functioning and overall well-being.
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Affiliation(s)
- Ilse Graat
- Department of Psychiatry, Amsterdam Universitair Medische Centra, University of Amsterdam, Amsterdam, the Netherlands.
| | - Roel Mocking
- Department of Psychiatry, Amsterdam Universitair Medische Centra, University of Amsterdam, Amsterdam, the Netherlands
| | - Martijn Figee
- Department of Psychiatry, Mount Sinai Hospital, New York, New York
| | - Nienke Vulink
- Department of Psychiatry, Amsterdam Universitair Medische Centra, University of Amsterdam, Amsterdam, the Netherlands
| | - Pelle de Koning
- Department of Psychiatry, Amsterdam Universitair Medische Centra, University of Amsterdam, Amsterdam, the Netherlands
| | - Pieter Ooms
- Department of Psychiatry, Amsterdam Universitair Medische Centra, University of Amsterdam, Amsterdam, the Netherlands
| | - Mariska Mantione
- Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Pepijn van den Munckhof
- Department of Neurosurgery, Amsterdam Universitair Medische Centra, University of Amsterdam, Amsterdam, the Netherlands
| | - Rick Schuurman
- Department of Neurosurgery, Amsterdam Universitair Medische Centra, University of Amsterdam, Amsterdam, the Netherlands
| | - Damiaan Denys
- Department of Psychiatry, Amsterdam Universitair Medische Centra, University of Amsterdam, Amsterdam, the Netherlands
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42
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Four Deep Brain Stimulation Targets for Obsessive-Compulsive Disorder: Are They Different? Biol Psychiatry 2021; 90:667-677. [PMID: 32951818 PMCID: PMC9569132 DOI: 10.1016/j.biopsych.2020.06.031] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 06/22/2020] [Accepted: 06/22/2020] [Indexed: 02/07/2023]
Abstract
Deep brain stimulation is a promising therapeutic approach for patients with treatment-resistant obsessive-compulsive disorder, a condition linked to abnormalities in corticobasal ganglia networks. Effective targets are placed in one of four subcortical areas with the goal of capturing prefrontal, anterior cingulate, and basal ganglia connections linked to the limbic system. These include the anterior limb of the internal capsule, the ventral striatum, the subthalamic nucleus, and a midbrain target. The goal of this review is to examine these 4 targets with respect to the similarities and differences of their connections. Following a review of the connections for each target based on anatomic studies in nonhuman primates, we examine the accuracy of diffusion magnetic resonance imaging tractography to replicate those connections in nonhuman primates, before evaluating the connections in the human brain based on diffusion magnetic resonance imaging tractography. Results demonstrate that the four targets generally involve similar connections, all of which are part of the internal capsule. Nonetheless, some connections are unique to each site. Delineating the similarities and differences across targets is a critical step for evaluating and comparing the effectiveness of each and how circuits contribute to the therapeutic outcome. It also underscores the importance that the terminology used for each target accurately reflects its position and its anatomic connections, so as to enable comparisons across clinical studies and for basic scientists to probe mechanisms underlying deep brain stimulation.
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Hembram M, Chaudhury S. Treatment Resistant Depression. EASTERN JOURNAL OF PSYCHIATRY 2021; 13:77-95. [DOI: 10.5005/ejp-13-1--2-77] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/19/2023]
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44
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Bouwens van der Vlis TAM, Duits A, van de Veerdonk MMGH, Mulders AEP, Schruers KRJ, Temel Y, Ackermans L, Leentjens AFG. Cognitive Outcome After Deep Brain Stimulation for Refractory Obsessive-Compulsive Disorder: A Systematic Review. Neuromodulation 2021; 25:185-194. [PMID: 34546638 DOI: 10.1111/ner.13534] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 06/23/2021] [Accepted: 07/28/2021] [Indexed: 11/30/2022]
Abstract
INTRODUCTION Deep brain stimulation (DBS) is an effective treatment for refractory obsessive-compulsive disorder (OCD). Neuropsychological assessment contributes to DBS treatment in several ways: it monitors the cognitive safety of the treatment, identifies beneficial or detrimental cognitive side effects and it could aid to explain variability in treatment outcome, and possibly the treatment's working mechanism(s). BACKGROUND This systematic review assessed the cognitive safety of DBS for OCD and explored whether changes in cognitive function may help explain its working mechanism(s). MATERIALS AND METHODS EMBASE, PubMed/Medline, Psycinfo, and the Cochrane Library were systematically searched for studies reporting cognitive outcomes following DBS for OCD. Searches were completed in November 2020. Included studies were appraised for study design and quality according to National Heart, Lung and Blood Institute (NHLBI) quality assessment tools. RESULTS Five randomized controlled trials and ten observational studies comprising a total of 178 patients were analyzed collectively. Variable outcomes of DBS were observed in the domains of attention, memory, executive functioning, and in particular cognitive flexibility. CONCLUSION Although individual studies generally do not report cognitive deterioration after DBS for OCD, the variability of study designs and the multitude of cognitive measures used, precluded a meta-analysis to confirm its safety, and recognition of a cognitive pattern through which the efficacy of DBS for OCD might be explained. In future, prospective studies should preferably include a standardized neuropsychological assessment battery specifically addressing executive functioning and have a longer-term follow-up in order to demonstrate the cognitive safety of the procedure. Such prospective and more uniform data collection may also contribute to our understanding of the working mechanisms of DBS in OCD.
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Affiliation(s)
| | - Annelien Duits
- Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, The Netherlands.,School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
| | | | - Anne E P Mulders
- Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Koen R J Schruers
- Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, The Netherlands.,School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.,Mondriaan Mental Health Center, Maastricht, The Netherlands
| | - Yasin Temel
- Department of Neurosurgery, Maastricht University Medical Centre, Maastricht, The Netherlands.,School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
| | - Linda Ackermans
- Department of Neurosurgery, Maastricht University Medical Centre, Maastricht, The Netherlands.,School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
| | - Albert F G Leentjens
- Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, The Netherlands.,School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
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Mar-Barrutia L, Real E, Segalás C, Bertolín S, Menchón JM, Alonso P. Deep brain stimulation for obsessive-compulsive disorder: A systematic review of worldwide experience after 20 years. World J Psychiatry 2021; 11:659-680. [PMID: 34631467 PMCID: PMC8474989 DOI: 10.5498/wjp.v11.i9.659] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 05/02/2021] [Accepted: 08/18/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Twenty years after its first use in a patient with obsessive-compulsive disorder (OCD), the results confirm that deep brain stimulation (DBS) is a promising therapy for patients with severe and resistant forms of the disorder. Nevertheless, many unknowns remain, including the optimal anatomical targets, the best stimulation parameters, the long-term (LT) effects of the therapy, and the clinical or biological factors associated with response. This systematic review of the articles published to date on DBS for OCD assesses the short and LT efficacy of the therapy and seeks to identify predictors of response.
AIM To summarize the existing knowledge on the efficacy and tolerability of DBS in treatment-resistant OCD.
METHODS A comprehensive search was conducted in the PubMed, Cochrane, Scopus, and ClinicalTrials.gov databases from inception to December 31, 2020, using the following strategy: “(Obsessive-compulsive disorder OR OCD) AND (deep brain stimulation OR DBS).” Clinical trials and observational studies published in English and evaluating the effectiveness of DBS for OCD in humans were included and screened for relevant information using a standardized collection tool. The inclusion criteria were as follows: a main diagnosis of OCD, DBS conducted for therapeutic purposes and variation in symptoms of OCD measured by the Yale-Brown Obsessive-Compulsive scale (Y-BOCS) as primary outcome. Data were analyzed with descriptive statistics.
RESULTS Forty articles identified by the search strategy met the eligibility criteria. Applying a follow-up threshold of 36 mo, 29 studies (with 230 patients) provided information on short-term (ST) response to DBS in, while 11 (with 155 patients) reported results on LT response. Mean follow-up period was 18.5 ± 8.0 mo for the ST studies and 63.7 ± 20.7 mo for the LT studies. Overall, the percentage of reduction in Y-BOCS scores was similar in ST (47.4%) and LT responses (47.2%) to DBS, but more patients in the LT reports met the criteria for response (defined as a reduction in Y-BOCS scores > 35%: ST, 60.6% vs LT, 70.7%). According to the results, the response in the first year predicts the extent to which an OCD patient will benefit from DBS, since the maximum symptom reduction was achieved in most responders in the first 12-14 mo after implantation. Reports indicate a consistent tendency for this early improvement to be maintained to the mid-term for most patients; but it is still controversial whether this improvement persists, increases or decreases in the long term. Three different patterns of LT response emerged from the analysis: 49.5% of patients had good and sustained response to DBS, 26.6% were non responders, and 22.5% were partial responders, who might improve at some point but experience relapses during follow-up. A significant improvement in depressive symptoms and global functionality was observed in most studies, usually (although not always) in parallel with an improvement in obsessive symptoms. Most adverse effects of DBS were mild and transient and improved after adjusting stimulation parameters; however, some severe adverse events including intracranial hemorrhages and infections were also described. Hypomania was the most frequently reported psychiatric side effect. The relationship between DBS and suicide risk is still controversial and requires further study. Finally, to date, no clear clinical or biological predictors of response can be established, probably because of the differences between studies in terms of the neuroanatomical targets and stimulation protocols assessed.
CONCLUSION The present review confirms that DBS is a promising therapy for patients with severe resistant OCD, providing both ST and LT evidence of efficacy.
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Affiliation(s)
- Lorea Mar-Barrutia
- OCD Clinical and Research Unit, Department of Psychiatry, Hospital de Bellvitge, Barcelona 08907, Spain
| | - Eva Real
- OCD Clinical and Research Unit, Department of Psychiatry, Hospital de Bellvitge, Barcelona 08907, Spain
- Bellvitge Biomedical Research Institute-IDIBELL, Barcelona 08907, Spain
- CIBERSAM (Centro de Investigación en Red de Salud Mental), Carlos III Health Institute, Madrid 28029, Spain
| | - Cinto Segalás
- OCD Clinical and Research Unit, Department of Psychiatry, Hospital de Bellvitge, Barcelona 08907, Spain
- Bellvitge Biomedical Research Institute-IDIBELL, Barcelona 08907, Spain
- CIBERSAM (Centro de Investigación en Red de Salud Mental), Carlos III Health Institute, Madrid 28029, Spain
| | - Sara Bertolín
- OCD Clinical and Research Unit, Department of Psychiatry, Hospital de Bellvitge, Barcelona 08907, Spain
| | - José Manuel Menchón
- OCD Clinical and Research Unit, Department of Psychiatry, Hospital de Bellvitge, Barcelona 08907, Spain
- Bellvitge Biomedical Research Institute-IDIBELL, Barcelona 08907, Spain
- CIBERSAM (Centro de Investigación en Red de Salud Mental), Carlos III Health Institute, Madrid 28029, Spain
- Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona 08907, Spain
| | - Pino Alonso
- OCD Clinical and Research Unit, Department of Psychiatry, Hospital de Bellvitge, Barcelona 08907, Spain
- Bellvitge Biomedical Research Institute-IDIBELL, Barcelona 08907, Spain
- CIBERSAM (Centro de Investigación en Red de Salud Mental), Carlos III Health Institute, Madrid 28029, Spain
- Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona 08907, Spain
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Georgiev D, Akram H, Jahanshahi M. Deep brain stimulation for psychiatric disorders: role of imaging in identifying/confirming DBS targets, predicting, and optimizing outcome and unravelling mechanisms of action. PSYCHORADIOLOGY 2021; 1:118-151. [PMID: 38665808 PMCID: PMC10917192 DOI: 10.1093/psyrad/kkab012] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 08/31/2021] [Accepted: 09/08/2021] [Indexed: 04/28/2024]
Abstract
Following the established application of deep brain stimulation (DBS) in the treatment of movement disorders, new non-neurological indications have emerged, such as for obsessive-compulsive disorders, major depressive disorder, dementia, Gilles de la Tourette Syndrome, anorexia nervosa, and addictions. As DBS is a network modulation surgical treatment, the development of DBS for both neurological and psychiatric disorders has been partly driven by advances in neuroimaging, which has helped explain the brain networks implicated. Advances in magnetic resonance imaging connectivity and electrophysiology have led to the development of the concept of modulating widely distributed, complex brain networks. Moreover, the increasing number of targets for treating psychiatric disorders have indicated that there may be a convergence of the effect of stimulating different targets for the same disorder, and the effect of stimulating the same target for different disorders. The aim of this paper is to review the imaging studies of DBS for psychiatric disorders. Imaging, and particularly connectivity analysis, offers exceptional opportunities to better understand and even predict the clinical outcomes of DBS, especially where there is a lack of objective biomarkers that are essential to properly guide DBS pre- and post-operatively. In future, imaging might also prove useful to individualize DBS treatment. Finally, one of the most important aspects of imaging in DBS is that it allows us to better understand the brain through observing the changes of the functional connectome under neuromodulation, which may in turn help explain the mechanisms of action of DBS that remain elusive.
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Affiliation(s)
- Dejan Georgiev
- Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, Queen Square, London, WC1N 3BG, UK
- Department of Neurology, University Medical Centre Ljubljana, Zaloška cesta 2, 1000 Ljubljana, Slovenia
- Artificial Intelligence Laboratory, Faculty of Computer and Information Science, University of Ljubljana, Večna pot 113, 1000 Ljubljana, Slovenia
| | - Harith Akram
- Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, Queen Square, London, WC1N 3BG, UK
| | - Marjan Jahanshahi
- Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, Queen Square, London, WC1N 3BG, UK
- The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, 611731, China
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Torres Díaz CV, Treu S, Strange B, Lara M, Navas M, Ezquiaga E, Zazo ES, Vicente JS, Muñiz I, Fernandez FS. Deep Brain Stimulation of the Nucleus Accumbens, Ventral Striatum, or Internal Capsule Targets for Medication-Resistant Obsessive-Compulsive Disorder: A Multicenter Study. World Neurosurg 2021; 155:e168-e176. [PMID: 34403796 DOI: 10.1016/j.wneu.2021.08.039] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 08/06/2021] [Accepted: 08/07/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND Deep brain stimulation of the nucleus accumbens, ventral striatum, or internal capsule region has shown a 45%-60% response rate in adults with severe treatment-refractory obsessive-compulsive disorder, regardless of which target is used. We sought to improve the effectiveness of deep brain stimulation by placing the electrode along a trajectory including these 3 targets, enabling a change of stimulation site depending on the patient's response. METHODS This study used the medical records of 14 patients from 4 different Spanish institutions: 7 from the Hospital Universitario La Princesa, 3 from the Hospital Universitario Central de Asturias, 2 from Hospital Universitario Fundación Jiménez Díaz, and 2 from Hospital Universitari Son Espases. All patients were operated on under the same protocol. Qualitative and quantitative data were collected. RESULTS Of 14 patients, 11 showed significant improvement in obsessive-compulsive disorder symptoms, as evident in a reduction ≥35% in Yale-Brown Obsessive Compulsive Scale scores following stimulation relative to preoperative scores. Seven patients responded to stimulation at the nucleus accumbens (the first area we set for stimulation), whereas 4 patients needed to have the active contact switched to the internal capsule to benefit from stimulation. CONCLUSIONS Deep brain stimulation of the nucleus accumbens, internal capsule, and ventral striatum significantly benefited our cohort of patients with medication-resistant obsessive-compulsive disorder. Electrode insertion through the 3 main targets might confer additional therapeutic efficacy.
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Affiliation(s)
- Cristina V Torres Díaz
- Department of Neurourgery, Hospital Universitario La Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
| | - Svenja Treu
- Laboratory for Clinical Neuroscience, Centre of Biomedical Technology, Universidad Politécnica de Madrid, Madrid, Spain
| | - Bryan Strange
- Laboratory for Clinical Neuroscience, Centre of Biomedical Technology, Universidad Politécnica de Madrid, Madrid, Spain
| | - Monica Lara
- Department of Neurosurgery, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
| | - Marta Navas
- Department of Neurourgery, Hospital Universitario La Princesa, Universidad Autónoma de Madrid, Madrid, Spain
| | - Elena Ezquiaga
- Department of Psychiatry, Hospital Universitario La Princesa, Universidad Autónoma de Madrid, Madrid, Spain
| | - Elisa Seijo Zazo
- Department of Psychiatry, Hospital Universitario Central de Asturias, Oviedo, Spain
| | | | - Isabel Muñiz
- Department of Psychology, Universidad Anáhuac Cancún, Cancún, Mexico
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Elias GJB, Loh A, Gwun D, Pancholi A, Boutet A, Neudorfer C, Germann J, Namasivayam A, Gramer R, Paff M, Lozano AM. Deep brain stimulation of the brainstem. Brain 2021; 144:712-723. [PMID: 33313788 DOI: 10.1093/brain/awaa374] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 07/31/2020] [Accepted: 08/17/2020] [Indexed: 01/02/2023] Open
Abstract
Deep brain stimulation (DBS) of the subthalamic nucleus, pallidum, and thalamus is an established therapy for various movement disorders. Limbic targets have also been increasingly explored for their application to neuropsychiatric and cognitive disorders. The brainstem constitutes another DBS substrate, although the existing literature on the indications for and the effects of brainstem stimulation remains comparatively sparse. The objective of this review was to provide a comprehensive overview of the pertinent anatomy, indications, and reported stimulation-induced acute and long-term effects of existing white and grey matter brainstem DBS targets. We systematically searched the published literature, reviewing clinical trial articles pertaining to DBS brainstem targets. Overall, 164 studies describing brainstem DBS were identified. These studies encompassed 10 discrete structures: periaqueductal/periventricular grey (n = 63), pedunculopontine nucleus (n = 48), ventral tegmental area (n = 22), substantia nigra (n = 9), mesencephalic reticular formation (n = 7), medial forebrain bundle (n = 8), superior cerebellar peduncles (n = 3), red nucleus (n = 3), parabrachial complex (n = 2), and locus coeruleus (n = 1). Indications for brainstem DBS varied widely and included central neuropathic pain, axial symptoms of movement disorders, headache, depression, and vegetative state. The most promising results for brainstem DBS have come from targeting the pedunculopontine nucleus for relief of axial motor deficits, periaqueductal/periventricular grey for the management of central neuropathic pain, and ventral tegmental area for treatment of cluster headaches. Brainstem DBS has also acutely elicited numerous motor, limbic, and autonomic effects. Further work involving larger, controlled trials is necessary to better establish the therapeutic potential of DBS in this complex area.
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Affiliation(s)
- Gavin J B Elias
- Division of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, Canada
| | - Aaron Loh
- Division of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, Canada
| | - Dave Gwun
- Division of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, Canada
| | - Aditya Pancholi
- Division of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, Canada
| | - Alexandre Boutet
- Division of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, Canada.,Joint Department of Medical Imaging, University of Toronto, Toronto, Canada
| | - Clemens Neudorfer
- Division of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, Canada
| | - Jürgen Germann
- Division of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, Canada
| | - Andrew Namasivayam
- Division of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, Canada
| | - Robert Gramer
- Division of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, Canada
| | - Michelle Paff
- Division of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, Canada
| | - Andres M Lozano
- Division of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, Canada
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Cheron J, Kerchove d'Exaerde AD. Drug addiction: from bench to bedside. Transl Psychiatry 2021; 11:424. [PMID: 34385417 PMCID: PMC8361217 DOI: 10.1038/s41398-021-01542-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 07/14/2021] [Accepted: 07/23/2021] [Indexed: 02/06/2023] Open
Abstract
Drug addiction is responsible for millions of deaths per year around the world. Still, its management as a chronic disease is shadowed by misconceptions from the general public. Indeed, drug consumers are often labelled as "weak", "immoral" or "depraved". Consequently, drug addiction is often perceived as an individual problem and not societal. In technical terms, drug addiction is defined as a chronic, relapsing disease resulting from sustained effects of drugs on the brain. Through a better characterisation of the cerebral circuits involved, and the long-term modifications of the brain induced by addictive drugs administrations, first, we might be able to change the way the general public see the patient who is suffering from drug addiction, and second, we might be able to find new treatments to normalise the altered brain homeostasis. In this review, we synthetise the contribution of fundamental research to the understanding drug addiction and its contribution to potential novel therapeutics. Mostly based on drug-induced modifications of synaptic plasticity and epigenetic mechanisms (and their behavioural correlates) and after demonstration of their reversibility, we tried to highlight promising therapeutics. We also underline the specific temporal dynamics and psychosocial aspects of this complex psychiatric disease adding parameters to be considered in clinical trials and paving the way to test new therapeutic venues.
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Affiliation(s)
- Julian Cheron
- Laboratory of Neurophysiology, ULB Neuroscience Institute, Université Libre de Bruxelles (ULB), Brussels, B-1070, Belgium
| | - Alban de Kerchove d'Exaerde
- Laboratory of Neurophysiology, ULB Neuroscience Institute, Université Libre de Bruxelles (ULB), Brussels, B-1070, Belgium.
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Byron N, Semenova A, Sakata S. Mutual Interactions between Brain States and Alzheimer's Disease Pathology: A Focus on Gamma and Slow Oscillations. BIOLOGY 2021; 10:707. [PMID: 34439940 PMCID: PMC8389330 DOI: 10.3390/biology10080707] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 07/17/2021] [Accepted: 07/21/2021] [Indexed: 12/26/2022]
Abstract
Brain state varies from moment to moment. While brain state can be defined by ongoing neuronal population activity, such as neuronal oscillations, this is tightly coupled with certain behavioural or vigilant states. In recent decades, abnormalities in brain state have been recognised as biomarkers of various brain diseases and disorders. Intriguingly, accumulating evidence also demonstrates mutual interactions between brain states and disease pathologies: while abnormalities in brain state arise during disease progression, manipulations of brain state can modify disease pathology, suggesting a therapeutic potential. In this review, by focusing on Alzheimer's disease (AD), the most common form of dementia, we provide an overview of how brain states change in AD patients and mouse models, and how controlling brain states can modify AD pathology. Specifically, we summarise the relationship between AD and changes in gamma and slow oscillations. As pathological changes in these oscillations correlate with AD pathology, manipulations of either gamma or slow oscillations can modify AD pathology in mouse models. We argue that neuromodulation approaches to target brain states are a promising non-pharmacological intervention for neurodegenerative diseases.
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Affiliation(s)
- Nicole Byron
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK
| | - Anna Semenova
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK
| | - Shuzo Sakata
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK
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