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Coelho DRA, Salvi JD, Vieira WF, Cassano P. Inflammation in obsessive-compulsive disorder: A literature review and hypothesis-based potential of transcranial photobiomodulation. J Neurosci Res 2024; 102:e25317. [PMID: 38459770 DOI: 10.1002/jnr.25317] [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: 08/01/2023] [Revised: 02/21/2024] [Accepted: 02/25/2024] [Indexed: 03/10/2024]
Abstract
Obsessive-compulsive disorder (OCD) is a disabling neuropsychiatric disorder that affects about 2%-3% of the global population. Despite the availability of several treatments, many patients with OCD do not respond adequately, highlighting the need for new therapeutic approaches. Recent studies have associated various inflammatory processes with the pathogenesis of OCD, including alterations in peripheral immune cells, alterations in cytokine levels, and neuroinflammation. These findings suggest that inflammation could be a promising target for intervention. Transcranial photobiomodulation (t-PBM) with near-infrared light is a noninvasive neuromodulation technique that has shown potential for several neuropsychiatric disorders. However, its efficacy in OCD remains to be fully explored. This study aimed to review the literature on inflammation in OCD, detailing associations with T-cell populations, monocytes, NLRP3 inflammasome components, microglial activation, and elevated proinflammatory cytokines such as TNF-α, CRP, IL-1β, and IL-6. We also examined the hypothesis-based potential of t-PBM in targeting these inflammatory pathways of OCD, focusing on mechanisms such as modulation of oxidative stress, regulation of immune cell function, reduction of proinflammatory cytokine levels, deactivation of neurotoxic microglia, and upregulation of BDNF gene expression. Our review suggests that t-PBM could be a promising, noninvasive intervention for OCD, with the potential to modulate underlying inflammatory processes. Future research should focus on randomized clinical trials to assess t-PBM's efficacy and optimal treatment parameters in OCD. Biomarker analyses and neuroimaging studies will be important in understanding the relationship between inflammatory modulation and OCD symptom improvement following t-PBM sessions.
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Affiliation(s)
- David Richer Araujo Coelho
- Division of Neuropsychiatry and Neuromodulation, Massachusetts General Hospital, Boston, Massachusetts, USA
- Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA
- Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Joshua D Salvi
- Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA
- Center for OCD and Related Disorders, Massachusetts General Hospital, Boston, Massachusetts, USA
- McLean Hospital, Belmont, Massachusetts, USA
| | - Willians Fernando Vieira
- Division of Neuropsychiatry and Neuromodulation, Massachusetts General Hospital, Boston, Massachusetts, USA
- Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA
- Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Paolo Cassano
- Division of Neuropsychiatry and Neuromodulation, Massachusetts General Hospital, Boston, Massachusetts, USA
- Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA
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2
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Coventry BS, Lawlor GL, Bagnati CB, Krogmeier C, Bartlett EL. Characterization and closed-loop control of infrared thalamocortical stimulation produces spatially constrained single-unit responses. PNAS NEXUS 2024; 3:pgae082. [PMID: 38725532 PMCID: PMC11079674 DOI: 10.1093/pnasnexus/pgae082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Accepted: 02/07/2024] [Indexed: 05/12/2024]
Abstract
Deep brain stimulation (DBS) is a powerful tool for the treatment of circuitopathy-related neurological and psychiatric diseases and disorders such as Parkinson's disease and obsessive-compulsive disorder, as well as a critical research tool for perturbing neural circuits and exploring neuroprostheses. Electrically mediated DBS, however, is limited by the spread of stimulus currents into tissue unrelated to disease course and treatment, potentially causing undesirable patient side effects. In this work, we utilize infrared neural stimulation (INS), an optical neuromodulation technique that uses near to midinfrared light to drive graded excitatory and inhibitory responses in nerves and neurons, to facilitate an optical and spatially constrained DBS paradigm. INS has been shown to provide spatially constrained responses in cortical neurons and, unlike other optical techniques, does not require genetic modification of the neural target. We show that INS produces graded, biophysically relevant single-unit responses with robust information transfer in rat thalamocortical circuits. Importantly, we show that cortical spread of activation from thalamic INS produces more spatially constrained response profiles than conventional electrical stimulation. Owing to observed spatial precision of INS, we used deep reinforcement learning (RL) for closed-loop control of thalamocortical circuits, creating real-time representations of stimulus-response dynamics while driving cortical neurons to precise firing patterns. Our data suggest that INS can serve as a targeted and dynamic stimulation paradigm for both open and closed-loop DBS.
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Affiliation(s)
- Brandon S Coventry
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA
- Center for Implantable Devices and the Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN 47907, USA
| | - Georgia L Lawlor
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA
- Center for Implantable Devices and the Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN 47907, USA
| | - Christina B Bagnati
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA
| | - Claudia Krogmeier
- Department of Computer Graphics Technology, Purdue University, West Lafayette, IN 47907, USA
| | - Edward L Bartlett
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA
- Center for Implantable Devices and the Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN 47907, USA
- Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA
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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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Monaco A, Cattaneo R, Di Nicolantonio S, Strada M, Altamura S, Ortu E. Central effects of trigeminal electrical stimulation. Cranio 2023:1-24. [PMID: 38032105 DOI: 10.1080/08869634.2023.2280153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2023]
Abstract
This is a review of the literature on the main neuromodulation techniques, focusing on the possibility of introducing sensory threshold ULFTENS into them. Electro neuromodulation techniques have been in use for many years as promising methods of therapy for cognitive and emotional disorders. One of the most widely used forms of stimulation for orofacial pain is transcutaneous trigeminal stimulation on three levels: supraorbital area, dorsal surface of the tongue, and anterior skin area of the tragus. The purpose of this review is to trigger interest on using dental ULFTENS as an additional trigeminal neurostimulation and neuromodulation technique in the context of TMD. In particular, we point out the possibility of using ULFTENS at a lower activation level than that required to trigger a muscle contraction that is capable of triggering effects at the level of the autonomic nervous system, with extreme ease of execution and few side effects.
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Affiliation(s)
- Annalisa Monaco
- MeSVA Department, Dental Unit, University of L'Aquila, L'Aquila, Italy
| | - Ruggero Cattaneo
- MeSVA Department, Dental Unit, University of L'Aquila, L'Aquila, Italy
| | | | - Marco Strada
- MeSVA Department, Dental Unit, University of L'Aquila, L'Aquila, Italy
| | - Serena Altamura
- MeSVA Department, Dental Unit, University of L'Aquila, L'Aquila, Italy
| | - Eleonora Ortu
- MeSVA Department, Dental Unit, University of L'Aquila, L'Aquila, Italy
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Coventry BS, Lawlor GL, Bagnati CB, Krogmeier C, Bartlett EL. Spatially specific, closed-loop infrared thalamocortical deep brain stimulation. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.10.04.560859. [PMID: 37904955 PMCID: PMC10614743 DOI: 10.1101/2023.10.04.560859] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/01/2023]
Abstract
Deep brain stimulation (DBS) is a powerful tool for the treatment of circuitopathy-related neurological and psychiatric diseases and disorders such as Parkinson's disease and obsessive-compulsive disorder, as well as a critical research tool for perturbing neural circuits and exploring neuroprostheses. Electrically-mediated DBS, however, is limited by the spread of stimulus currents into tissue unrelated to disease course and treatment, potentially causing undesirable patient side effects. In this work, we utilize infrared neural stimulation (INS), an optical neuromodulation technique that uses near to mid-infrared light to drive graded excitatory and inhibitory responses in nerves and neurons, to facilitate an optical and spatially constrained DBS paradigm. INS has been shown to provide spatially constrained responses in cortical neurons and, unlike other optical techniques, does not require genetic modification of the neural target. We show that INS produces graded, biophysically relevant single-unit responses with robust information transfer in thalamocortical circuits. Importantly, we show that cortical spread of activation from thalamic INS produces more spatially constrained response profiles than conventional electrical stimulation. Owing to observed spatial precision of INS, we used deep reinforcement learning for closed-loop control of thalamocortical circuits, creating real-time representations of stimulus-response dynamics while driving cortical neurons to precise firing patterns. Our data suggest that INS can serve as a targeted and dynamic stimulation paradigm for both open and closed-loop DBS.
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Affiliation(s)
- Brandon S Coventry
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN USA
- Center for Implantable Devices and the Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN USA
| | - Georgia L Lawlor
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN USA
- Center for Implantable Devices and the Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN USA
| | - Christina B Bagnati
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN USA
| | - Claudia Krogmeier
- Department of Computer Graphics Technology, Purdue University, West Lafayette, IN USA
| | - Edward L Bartlett
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN USA
- Center for Implantable Devices and the Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN USA
- Department of Biological Sciences, Purdue University, West Lafayette, IN USA
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Strouphauer ER, Morris OJ, Soileau KJ, Wiese AD, Quast T, Goodman WK, Sheth SA, Wojcik KD, Guzick AG, Storch EA. Economic Analyses of Obsessive-Compulsive Disorder Interventions: A Systematic Review. PHARMACOECONOMICS 2023; 41:499-527. [PMID: 36840747 DOI: 10.1007/s40273-023-01250-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 02/06/2023] [Indexed: 05/10/2023]
Abstract
BACKGROUND Obsessive-compulsive disorder (OCD) is a neuropsychiatric condition featuring patterns of obsessions, compulsions, and avoidant behaviors that are often time consuming and distressing to affected individuals. Cognitive-behavioral therapy (CBT) with exposure and response prevention and/or serotonin reuptake inhibitors are first-line treatments for OCD, though other therapeutic interventions may serve as economically practical modalities under various circumstances. Exploring and understanding the cost effectiveness of all indicated OCD interventions are important to inform therapeutic decisions and provide quality patient-centered care at a cost that is not burdensome to the patient and/or healthcare system. METHODS A systematic literature review was performed and studies were extracted from PubMed, Embase, Ovid MEDLINE, and Cochrane. All cost-effectiveness studies that included economic analyses with respect to OCD treatment modalities and were written in English and published between January 2010 and July 2022 were eligible for inclusion in the present study. We report a narrative synthesis of the findings and quality appraisal of the selected references. RESULTS Of the 707 references returned in the literature search, a total of 18 cost-effectiveness studies were included for review. Compared with treatment as usual, several studies reported clinical superiority and cost effectiveness of Internet-based CBT programs for adults and children with OCD at various willingness-to-pay thresholds and economic reference indicators, though cost effectiveness relative to in-person CBT with exposure and response prevention is unclear and estimates of efficacy are likely lower for Internet-based CBT. One study favored the cost utility of serotonin reuptake inhibitor monotherapy over CBT with exposure and response prevention although efficacy estimates of the former tend to be lower, and relative cost differences were low. Five studies evaluated the cost effectiveness of high-intensity neuroaugmentation, including deep brain stimulation and stereotactic radiosurgical capsulotomy, in the context of treatment-refractory OCD. CONCLUSIONS Despite the relatively high prevalence of OCD worldwide, cost-effectiveness data for therapeutic modalities remain sparse. Because of the chronic nature of OCD, the cost of treatment accumulates and may lead to a significant financial burden over time, particularly when non-evidence-based interventions are used. However, several alternative therapeutic modalities hold promise for economic practicality without significant sacrifice in clinical efficacy. Future studies are necessary to directly compare the cost effectiveness of such therapeutic alternatives with the current standard of care, CBT with exposure and response prevention.
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Affiliation(s)
- Emily R Strouphauer
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, One Baylor Plaza, MS: 350, Houston, TX, 77030, USA
| | - Olivia J Morris
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, One Baylor Plaza, MS: 350, Houston, TX, 77030, USA
| | - Keaton J Soileau
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, One Baylor Plaza, MS: 350, Houston, TX, 77030, USA
| | - Andrew D Wiese
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, One Baylor Plaza, MS: 350, Houston, TX, 77030, USA
| | - Troy Quast
- College of Public Health, University of South Florida, Tampa, FL, USA
| | - Wayne K Goodman
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, One Baylor Plaza, MS: 350, Houston, TX, 77030, USA
| | - Sameer A Sheth
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA
| | - Katharine D Wojcik
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, One Baylor Plaza, MS: 350, Houston, TX, 77030, USA
| | - Andrew G Guzick
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, One Baylor Plaza, MS: 350, Houston, TX, 77030, USA
| | - Eric A Storch
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, One Baylor Plaza, MS: 350, Houston, TX, 77030, USA.
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Chandrabhatla AS, Pomeraniec IJ, Horgan TM, Wat EK, Ksendzovsky A. Landscape and future directions of machine learning applications in closed-loop brain stimulation. NPJ Digit Med 2023; 6:79. [PMID: 37106034 PMCID: PMC10140375 DOI: 10.1038/s41746-023-00779-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 02/17/2023] [Indexed: 04/29/2023] Open
Abstract
Brain stimulation (BStim) encompasses multiple modalities (e.g., deep brain stimulation, responsive neurostimulation) that utilize electrodes implanted in deep brain structures to treat neurological disorders. Currently, BStim is primarily used to treat movement disorders such as Parkinson's, though indications are expanding to include neuropsychiatric disorders like depression and schizophrenia. Traditional BStim systems are "open-loop" and deliver constant electrical stimulation based on manually-determined parameters. Advancements in BStim have enabled development of "closed-loop" systems that analyze neural biomarkers (e.g., local field potentials in the sub-thalamic nucleus) and adjust electrical modulation in a dynamic, patient-specific, and energy efficient manner. These closed-loop systems enable real-time, context-specific stimulation adjustment to reduce symptom burden. Machine learning (ML) has emerged as a vital component in designing these closed-loop systems as ML models can predict / identify presence of disease symptoms based on neural activity and adaptively learn to modulate stimulation. We queried the US National Library of Medicine PubMed database to understand the role of ML in developing closed-loop BStim systems to treat epilepsy, movement disorders, and neuropsychiatric disorders. Both neural and non-neural network ML algorithms have successfully been leveraged to create closed-loop systems that perform comparably to open-loop systems. For disorders in which the underlying neural pathophysiology is relatively well understood (e.g., Parkinson's, essential tremor), most work has involved refining ML models that can classify neural signals as aberrant or normal. The same is seen for epilepsy, where most current research has focused on identifying optimal ML model design and integrating closed-loop systems into existing devices. For neuropsychiatric disorders, where the underlying pathologic neural circuitry is still being investigated, research is focused on identifying biomarkers (e.g., local field potentials from brain nuclei) that ML models can use to identify onset of symptoms and stratify severity of disease.
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Affiliation(s)
- Anirudha S Chandrabhatla
- School of Medicine, University of Virginia Health Sciences Center, Charlottesville, VA, 22903, USA
| | - I Jonathan Pomeraniec
- Surgical Neurology Branch, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 20892, USA.
- Department of Neurosurgery, University of Virginia Health Sciences Center, Charlottesville, VA, 22903, USA.
| | - Taylor M Horgan
- School of Medicine, University of Virginia Health Sciences Center, Charlottesville, VA, 22903, USA
| | - Elizabeth K Wat
- School of Medicine, University of Virginia Health Sciences Center, Charlottesville, VA, 22903, USA
| | - Alexander Ksendzovsky
- Department of Neurosurgery, University of Maryland Medical System, Baltimore, MD, 21201, USA
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Zhang A, Qiao D, Wang Y, Yang C, Wang Y, Sun N, Hu X, Liu Z, Zhang K. Distinguishing between bipolar depression and unipolar depression based on the reward circuit activities and clinical characteristics: A machine learning analysis. J Affect Disord 2023; 327:46-53. [PMID: 36708957 DOI: 10.1016/j.jad.2023.01.080] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 12/31/2022] [Accepted: 01/21/2023] [Indexed: 01/26/2023]
Abstract
BACKGROUND Differentiating bipolar depression (BD) from unipolar depression (UD) is a major clinical challenge. Identifying the potential classifying biomarkers between these two diseases is vital to optimize personalized management of depressed individuals. METHODS Here, we aimed to integrate neuroimaging and clinical data with machine learning method to classify BD and UD at the individual level. Data were collected from 31 healthy controls (HC group) and 80 depressive patients with an average follow-up period of 7.51 years. Of these patients, 32 got diagnosis conversion from major depressive disorder (MDD) to BD (BD group) and 48 remain persistent diagnosis of MDD (MDD group). Using graph theory and functional connectivity (FC) analysis, we investigated the differences in reward circuit properties among three groups. Then we applied a support vector machine and leave-one-out cross-validation methods to classify BD and UD patients based on neuroimaging and clinical data. RESULTS Compared with MDD and HC, BD showed decreased degree centrality of right mediodorsal thalamus (MD) and nodal efficiency (NE) of left ventral pallidum. Compared with BD and HC, MDD showed decreased NE of right MD and increased FC between right MD and bilateral dorsolateral prefrontal cortex and left ventromedial prefrontal cortex. Notably, the classifier obtained high classification accuracies (87.50 %) distinguishing BD and UD patients based on reward circuit properties and clinical features. LIMITATIONS The classifying model requires out-of-sample replication analysis. CONCLUSION The reward circuit dysfunction can not only provide additional information to assist clinical differential diagnosis, but also in turn informed treatment decision of depressive patients.
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Affiliation(s)
- Aixia Zhang
- Department of Psychiatry, the First Hospital of Shanxi Medical University, Taiyuan 030001, China
| | - Dan Qiao
- Department of Psychiatry, the First Hospital of Shanxi Medical University, Taiyuan 030001, China
| | - Yuchen Wang
- Department of Psychiatry, the First Hospital of Shanxi Medical University, Taiyuan 030001, China
| | - Chunxia Yang
- Department of Psychiatry, the First Hospital of Shanxi Medical University, Taiyuan 030001, China
| | - Yanfang Wang
- Department of Psychiatry, the First Hospital of Shanxi Medical University, Taiyuan 030001, China
| | - Ning Sun
- Department of Psychiatry, the First Hospital of Shanxi Medical University, Taiyuan 030001, China
| | - Xiaodong Hu
- Department of Psychiatry, the First Hospital of Shanxi Medical University, Taiyuan 030001, China
| | - Zhifen Liu
- Department of Psychiatry, the First Hospital of Shanxi Medical University, Taiyuan 030001, China.
| | - Kerang Zhang
- Department of Psychiatry, the First Hospital of Shanxi Medical University, Taiyuan 030001, China.
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Derksen M, Zuidinga B, van der Veer M, Rhemrev V, Jolink L, Reneman L, Nederveen A, Forstmann B, Feenstra M, Willuhn I, Denys D. A comparison of how deep brain stimulation in two targets with anti-compulsive efficacy modulates brain activity using fMRI in awake rats. Psychiatry Res Neuroimaging 2023; 330:111611. [PMID: 36796237 DOI: 10.1016/j.pscychresns.2023.111611] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 12/21/2022] [Accepted: 02/06/2023] [Indexed: 02/11/2023]
Abstract
Deep brain stimulation (DBS) is an established neuromodulatory intervention against otherwise treatment-refractory obsessive-compulsive disorder (OCD). Several DBS targets, all of which are part of brain networks connecting basal ganglia and prefrontal cortex, alleviate OCD symptoms. Stimulation of these targets is thought to unfold its therapeutic effect by modulation of network activity through internal capsule (IC) connections. Research into DBS-induced network changes and the nature of IC-related effects of DBS in OCD is needed to further improve DBS. Here, we studied the effects of DBS at the ventral medial striatum (VMS) and IC on blood-oxygen level dependent (BOLD) responses in awake rats using functional magnetic resonance imaging (fMRI). BOLD-signal intensity was measured in five regions of interest (ROIs): medial and orbital prefrontal cortex, nucleus accumbens (NAc), IC area, and mediodorsal thalamus. In previous rodent studies, stimulation at both target locations resulted in a reduction of OCD-like behavior and activation of prefrontal cortical areas. Therefore, we hypothesized that stimulation at both targets would result in partially overlapping BOLD responses. Both differential and overlapping activity between VMS and IC stimulation was found. Stimulating the caudal part of the IC resulted in activation around the electrode, while stimulating the rostral part of the IC resulted in increased cross-correlations between the IC area, orbitofrontal cortex, and NAc. Stimulation of the dorsal part of the VMS resulted in increased activity in the IC area, suggesting this area is activated during both VMS and IC stimulation. This activation is also indicative of VMS-DBS impacting corticofugal fibers running through the medial caudate into the anterior IC, and both VMS and IC DBS might act on these fibers to induce OCD-reducing effects. These results show that rodent fMRI with simultaneous electrode stimulation is a promising approach to study the neural mechanisms of DBS. Comparing the effects of DBS in different target areas has the potential to improve our understanding of the neuromodulatory changes that take place across various networks and connections in the brain. Performing this research in animal disease models will lead to translational insights in the mechanisms underlying DBS, and can aid improvement and optimization of DBS in patient populations.
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Affiliation(s)
- Maik Derksen
- The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands; Department of Psychiatry, Amsterdam University Medical Centers (location AMC), University of Amsterdam, Amsterdam, The Netherlands
| | - Birte Zuidinga
- The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands
| | - Marijke van der Veer
- The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands
| | - Valerie Rhemrev
- The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands
| | - Linda Jolink
- The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands
| | - Liesbeth Reneman
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers (location AMC), University of Amsterdam, Amsterdam, The Netherlands
| | - Aart Nederveen
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers (location AMC), University of Amsterdam, Amsterdam, The Netherlands
| | - Birte Forstmann
- University of Amsterdam, Integrative Model-based Cognitive Neuroscience Research Unit, Amsterdam, The Netherlands
| | - Matthijs Feenstra
- The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands; Department of Psychiatry, Amsterdam University Medical Centers (location AMC), University of Amsterdam, Amsterdam, The Netherlands
| | - Ingo Willuhn
- The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands; Department of Psychiatry, Amsterdam University Medical Centers (location AMC), University of Amsterdam, Amsterdam, The Netherlands
| | - Damiaan Denys
- The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands; Department of Psychiatry, Amsterdam University Medical Centers (location AMC), University of Amsterdam, Amsterdam, The Netherlands
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10
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Deep brain stimulation of the subthalamic nucleus to improve symptoms and cognitive functions in patients with refractory obsessive-compulsive disorder: a longitudinal study. Neurol Sci 2023:10.1007/s10072-023-06614-1. [PMID: 36849693 DOI: 10.1007/s10072-023-06614-1] [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: 11/11/2021] [Accepted: 01/10/2023] [Indexed: 03/01/2023]
Abstract
There are conflicting results regarding the effect of deep brain stimulation (DBS) of different regions on the cognitive functions of patients with severe refractory obsessive-compulsive disorder (OCD). Moreover, it is not yet clear whether the rate of improvement in obsession-compulsion symptoms and cognitive functions following DBS is interrelated. We investigated the effect of the subthalamic nucleus (STN)-DBS on both the severity of symptoms and cognitive functions of patients and also investigated the possible interrelationship between the two. Twelve patients (10 males and two females; 56.17 ± 4.52 years old) were assessed before and 1 month and 3 months after the DBS surgery using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the N-Back, the selective and divided attention (SDA), the Tower of London (TOL), and the Wisconsin Card Sorting (WCS) tests. We found that the severity of symptoms and cognitive functions improved significantly after DBS and this effect lasted at least up to 3 months. Furthermore, it was revealed that the severity of symptoms and cognitive profiles of patients were significantly correlated. Compulsion severity had the highest correlation with perseveration errors, while obsession severity was most correlated with the number of n-back errors. Based on our findings, it seems that the STN acts at least to some extent as a common functional/anatomical ground for the severity of symptoms and cognitive functions of patients with severe refractory OCD, and it can probably be considered as the region of interest for DBS in this group of patients.
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Swierkosz-Lenart K, Dos Santos JFA, Elowe J, Clair AH, Bally JF, Riquier F, Bloch J, Draganski B, Clerc MT, Pozuelo Moyano B, von Gunten A, Mallet L. Therapies for obsessive-compulsive disorder: Current state of the art and perspectives for approaching treatment-resistant patients. Front Psychiatry 2023; 14:1065812. [PMID: 36873207 PMCID: PMC9978117 DOI: 10.3389/fpsyt.2023.1065812] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 01/25/2023] [Indexed: 02/18/2023] Open
Abstract
Even though obsessive compulsive disorder (OCD) is one of the ten most disabling diseases according to the WHO, only 30-40% of patients suffering from OCD seek specialized treatment. The currently available psychotherapeutic and pharmacological approaches, when properly applied, prove ineffective in about 10% of cases. The use of neuromodulation techniques, especially Deep Brain Stimulation, is highly promising for these clinical pictures and knowledge in this domain is constantly evolving. The aim of this paper is to provide a summary of the current knowledge about OCD treatment, while also discussing the more recent proposals for defining resistance.
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Affiliation(s)
- Kevin Swierkosz-Lenart
- Department of Psychiatry, Service Universitaire de Psychiatrie de l’Age Avancé (SUPAA), Centre Hospitalier Universitaire Vaudois, Prilly, Switzerland
| | | | - Julien Elowe
- Department of Psychiatry, Lausanne University Hospital, University of Lausanne, West Sector, Prangins, Switzerland
- Department of Psychiatry, Lausanne University Hospital, University of Lausanne, North Sector, Yverdon-les-Bains, Switzerland
| | - Anne-Hélène Clair
- Sorbonne University, UPMC Paris 06 University, INSERM, CNRS, Institut du Cerveau et de la Moelle Épinière, Paris, France
| | - Julien F. Bally
- Department of Clinical Neurosciences, Service of Neurology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Françoise Riquier
- Department of Clinical Neuroscience, Service of Neurosurgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland
| | - Jocelyne Bloch
- Department of Clinical Neuroscience, Service of Neurosurgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland
| | - Bogdan Draganski
- Laboratory for Research in Neuroimaging (LREN), Department of Clinical Neurosciences, Centre for Research in Neurosciences, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
| | - Marie-Thérèse Clerc
- Department of Psychiatry, Service Universitaire de Psychiatrie de l’Age Avancé (SUPAA), Centre Hospitalier Universitaire Vaudois, Prilly, Switzerland
| | - Beatriz Pozuelo Moyano
- Department of Psychiatry, Service Universitaire de Psychiatrie de l’Age Avancé (SUPAA), Centre Hospitalier Universitaire Vaudois, Prilly, Switzerland
| | - Armin von Gunten
- Department of Psychiatry, Service Universitaire de Psychiatrie de l’Age Avancé (SUPAA), Centre Hospitalier Universitaire Vaudois, Prilly, Switzerland
| | - Luc Mallet
- Department of Mental Health and Psychiatry, Geneva University Hospital, Geneva, Switzerland
- Univ Paris-Est Créteil, DMU IMPACT, Département Médical-Universitaire de Psychiatrie et d’Addictologie, Hôpitaux Universitaires Henri Mondor - Albert Chenevier, Assistance Publique-Hôpitaux de Paris, Créteil, France
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Paris, France
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12
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Investigating Deep Brain Stimulation of the Habenula: A Review of Clinical Studies. Neuromodulation 2023; 26:292-301. [PMID: 35840520 DOI: 10.1016/j.neurom.2022.05.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 05/19/2022] [Indexed: 02/07/2023]
Abstract
OBJECTIVES The aim of this study was to examine the current scientific literature on deep brain stimulation (DBS) targeting the habenula for the treatment of neuropsychiatric disorders including schizophrenia, major depressive disorder, and obsessive-compulsive disorder (OCD). MATERIALS AND METHODS Two authors performed independent data base searches using the PubMed, Cochrane, PsycINFO, and Web of Science search engines. The data bases were searched for the query ("deep brain stimulation" and "habenula"). The inclusion criteria involved screening for human clinical trials written in English and published from 2007 to 2020. From the eligible studies, data were collected on the mean age, sex, number of patients included, and disorder treated. Patient outcomes of each study were summarized. RESULTS The search yielded six studies, which included 11 patients in the final analysis. Treated conditions included refractory depression, bipolar disorder, OCD, schizophrenia, and major depressive disorder. Patients with bipolar disorder unmedicated for at least two months had smaller habenula volumes than healthy controls. High-frequency stimulation of the lateral habenula attenuated the rise of serotonin in the dorsal raphe nucleus for treating depression. Bilateral habenula DBS and patient OCD symptoms were reduced and maintained at one-year follow up. Low- and high-frequency stimulation DBS can simulate input paths to the lateral habenula to treat addiction, including cocaine addiction. More data are needed to draw conclusions as to the impact of DBS for schizophrenia and obesity. CONCLUSIONS The habenula is a novel target that could aid in reducing neuropsychiatric symptoms and should be considered in circuit-specific investigation of neuromodulation for psychiatric disorders. More information needs to be gathered and assessed before this treatment is fully approved for treatment of neuropsychiatric conditions.
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13
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Haber SN, Lehman J, Maffei C, Yendiki A. The rostral zona incerta: a subcortical integrative hub and potential DBS target for OCD. Biol Psychiatry 2023; 93:1010-1022. [PMID: 37055285 DOI: 10.1016/j.biopsych.2023.01.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 12/13/2022] [Accepted: 01/08/2023] [Indexed: 01/20/2023]
Abstract
BACKGROUND The zona incerta (ZI) is involved in mediating survival behaviors and is connected to a wide range of cortical and subcortical structures, including key basal ganglia nuclei. Based on these connections and their links to behavioral modulation, we propose that the ZI is a connectional hub for mediating between top-down and bottom-up control and a possible target for deep brain stimulation for obsessive-compulsive disorder. METHODS We analyzed the trajectory of cortical fibers to the ZI in nonhuman and human primates based on tracer injections in monkeys and high-resolution diffusion magnetic resonance imaging in humans. The organization of cortical and subcortical connections within the ZI were identified in the nonhuman primate studies. RESULTS Monkey anatomical data and human diffusion magnetic resonance imaging data showed a similar trajectory of fibers/streamlines to the ZI. Prefrontal cortex/anterior cingulate cortex terminals all converged within the rostral ZI, with dorsal and lateral areas being most prominent. Motor areas terminated caudally. Dense subcortical reciprocal connections included the thalamus, medial hypothalamus, substantia nigra/ventral tegmental area, reticular formation, and pedunculopontine nucleus and a dense nonreciprocal projection to the lateral habenula. Additional connections included the amygdala, dorsal raphe nucleus, and periaqueductal gray. CONCLUSIONS Dense connections with dorsal and lateral prefrontal cortex/anterior cingulate cortex cognitive control areas and the lateral habenula and the substantia nigra/ventral tegmental area, coupled with inputs from the amygdala, hypothalamus, and brainstem, suggest that the rostral ZI is a subcortical hub positioned to modulate between top-down and bottom-up control. A deep brain stimulation electrode placed in the rostral ZI would not only involve connections common to other deep brain stimulation sites but also capture several critically distinctive connections.
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Affiliation(s)
- Suzanne N Haber
- Department of Pharmacology & Physiology, University of Rochester School of Medicine and Dentistry, Rochester, New York; Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts.
| | - Julia Lehman
- Department of Pharmacology & Physiology, University of Rochester School of Medicine and Dentistry, Rochester, New York
| | - Chiara Maffei
- Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Anastasia Yendiki
- Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
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14
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Obsessive-compulsive symptoms are negatively correlated with motor severity in patients with generalized dystonia. Sci Rep 2022; 12:20350. [PMID: 36437372 PMCID: PMC9701695 DOI: 10.1038/s41598-022-24826-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Accepted: 11/21/2022] [Indexed: 11/28/2022] Open
Abstract
We aimed to clarify the correlations between motor symptoms and obsessive-compulsive symptoms and between the volumes of basal ganglia components and obsessive-compulsive symptoms. We retrospectively included 14 patients with medically intractable, moderate and severe generalized dystonia. The Burke-Fahn-Marsden Dystonia Rating Scale and Maudsley Obsessional Compulsive Inventory were used to evaluate the severity of dystonia and obsessive-compulsive symptoms, respectively. Patients with generalized dystonia were divided into two groups; patients whose Maudsley Obsessional Compulsive Inventory score was lower than 13 (Group 1) and 13 or more (Group 2). Additionally, the total Maudsley Obsessional Compulsive Inventory scores in patients with dystonia were significantly higher than normal volunteers' scores (p = 0.025). Unexpectedly, Group 2 (high Maudsley Obsessional Compulsive Inventory scores) showed milder motor symptoms than Group 1 (low Maudsley Obsessional Compulsive Inventory scores) (p = 0.016). "Checking" rituals had a strong and significant negative correlation with the Burke-Fahn-Marsden Dystonia Rating Scale (ρ = - 0.71, p = 0.024) and a strong positive correlation with the volumes of both sides of the nucleus accumbens (right: ρ = 0.72, p = 0.023; left: ρ = 0.70, p = 0.034). Our results may provide insights into the pathogenesis of obsessive-compulsive disorder and dystonia.
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15
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Banks GP, Heilbronner SR, Goodman W, Sheth SA. A population-normalized tractographic fiber atlas of the anterior limb of the internal capsule: relevance to surgical neuromodulation. J Neurosurg 2022; 137:1278-1288. [PMID: 35395627 DOI: 10.3171/2022.1.jns211935] [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: 08/29/2021] [Accepted: 01/31/2022] [Indexed: 11/06/2022]
Abstract
OBJECTIVE The anterior limb of the internal capsule (ALIC) is a white matter highway that connects several subcortical structures to the prefrontal cortex. Although surgical interventions in the ALIC have been used to treat a number of psychiatric illnesses, there is significant debate regarding what fibers are targeted for intervention. This debate is partially due to an incomplete understanding of connectivity in the region. METHODS To better understand this complex structure, the authors employed a novel tractography-based approach to examine how fibers from the thalamus and subthalamic nucleus (STN) traverse the ALIC. Furthermore, the authors analyzed connections from the medial dorsal nucleus, anterior nucleus, and ventral anterior nucleus of the thalamus. RESULTS The results showed that there is an organizational gradient of thalamic fibers medially and STN fibers laterally in the ALIC that fades more anteriorly. These findings, in combination with the known corticotopic organization described by previous studies, allow for a more thorough understanding of the organization of the white matter fibers in the ALIC. CONCLUSIONS These results are important for understanding and targeting of neuromodulatory therapies in the ALIC and may help explain why differences in therapeutic effect are observed for different areas of the ALIC.
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Affiliation(s)
- Garrett P Banks
- 1Department of Neurosurgery, Columbia University Medical Center, New York, New York
| | - Sarah R Heilbronner
- 2Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota
| | - Wayne Goodman
- 3Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas; and
| | - Sameer A Sheth
- 4Department of Neurosurgery, Baylor College of Medicine, Houston, Texas
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16
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Ruan H, Wang Y, Li Z, Tong G, Wang Z. A Systematic Review of Treatment Outcome Predictors in Deep Brain Stimulation for Refractory Obsessive-Compulsive Disorder. Brain Sci 2022; 12:brainsci12070936. [PMID: 35884742 PMCID: PMC9316868 DOI: 10.3390/brainsci12070936] [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: 05/24/2022] [Revised: 07/06/2022] [Accepted: 07/15/2022] [Indexed: 12/04/2022] Open
Abstract
Obsessive-compulsive disorder (OCD) is a chronic and debilitating mental disorder. Deep brain stimulation (DBS) is a promising approach for refractory OCD patients. Research aiming at treatment outcome prediction is vital to provide optimized treatments for different patients. The primary purpose of this systematic review was to collect and synthesize studies on outcome prediction of OCD patients with DBS implantations in recent years. This systematic review (PROSPERO registration number: CRD42022335585) followed the PRISMA (Preferred Reporting Items for Systematic Review and Meta-analysis) guidelines. The search was conducted using three different databases with the following search terms related to OCD and DBS. We identified a total of 3814 articles, and 17 studies were included in our review. A specific tract confirmed by magnetic resonance imaging (MRI) was predictable for DBS outcome regardless of implant targets, but inconsistencies still exist. Current studies showed various ways of successful treatment prediction. However, considering the heterogeneous results, we hope that future studies will use larger cohorts and more precise approaches for predictors and establish more personalized ways of DBS surgeries.
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Affiliation(s)
- Hanyang Ruan
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China; (H.R.); (Y.W.); (Z.L.); (G.T.)
| | - Yang Wang
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China; (H.R.); (Y.W.); (Z.L.); (G.T.)
| | - Zheqin Li
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China; (H.R.); (Y.W.); (Z.L.); (G.T.)
| | - Geya Tong
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China; (H.R.); (Y.W.); (Z.L.); (G.T.)
| | - Zhen Wang
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China; (H.R.); (Y.W.); (Z.L.); (G.T.)
- Institute of Psychological and Behavioral Science, Shanghai Jiao Tong University, Shanghai 200030, China
- Shanghai Key Laboratory of Psychotic Disorders (No. 13dz2260500), Shanghai 200030, China
- Correspondence: ; Tel.: +86-180-1731-1286
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17
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The Efficacy and Safety of Deep Brain Stimulation of Combined Anterior Limb of Internal Capsule and Nucleus Accumbens (ALIC/NAcc-DBS) for Treatment-Refractory Obsessive-Compulsive Disorder: Protocol of a Multicenter, Randomized, and Double-Blinded Study. Brain Sci 2022; 12:brainsci12070933. [PMID: 35884739 PMCID: PMC9313119 DOI: 10.3390/brainsci12070933] [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: 06/08/2022] [Revised: 07/10/2022] [Accepted: 07/12/2022] [Indexed: 02/05/2023] Open
Abstract
Backgrounds: Deep brain stimulation (DBS) is an emerging and promising therapeutic approach for treatment-refractory obsessive-compulsive disorder (OCD). The most common DBS targets include the anterior limb of internal capsule (ALIC) and nucleus accumbens (NAcc). This protocol aims to explore the efficacy and safety of the combined ALIC- and NAcc-DBS for treatment-refractory OCD. Methods: We will recruit 64 patients with refractory OCD from six centers, randomly allocate them to active and sham-stimulation groups through a three-month double-blind phase, then enter a three-month open-label phase. In the open-label stage, both groups experience real stimulation. Outcome measures: The primary outcome will be the efficacy and safety of combined ALIC- and NAcc-DBS, determined by treatment response rate between the active and sham-stimulation groups at the double-blind stage and spontaneously reported adverse events. The secondary outcomes are comparisons of change in Y–BOCS, CGI, HAMD, and HAMA scores at the third and sixth months compared to baseline between the active and sham-control groups, as well as the scores of the third month minus the sixth month between the two groups.
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18
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Tomskiy AA, Poddubskaya AA, Gamaleya AA, Zaitsev OS. Neurosurgical management of Tourette syndrome: A literature review and analysis of a case series treated with deep brain stimulation. PROGRESS IN BRAIN RESEARCH 2022; 272:41-72. [PMID: 35667806 DOI: 10.1016/bs.pbr.2022.03.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Tourette syndrome (TS) is a heterogeneous disorder, which clinical presentation includes both multiple motor and vocal tics and commonly associated psychiatric conditions (obsessive-compulsive disorder, attention deficit hyperactivity disorder, depression, anxiety, etc.). Treatment options primarily consist of non-pharmacological interventions (habit reversal training, relaxation techniques, cognitive behavioral therapy, and social rehabilitation) and pharmacotherapy. In case of the intractable forms, neurosurgical treatment may be considered, primarily deep brain stimulation (DBS). DBS appear to be effective in medically intractable TS patients, although, the preferential brain target is still not defined. The majority of studies describe small number of cases and the issues of appropriate patient selection and ethics remain to be clarified. In this article, we review the main points in management of TS, discuss possible indications and contraindications for neurosurgical treatment, and analyze our experience of DBS in a case series of refractory TS patients with the focus on target selection and individual outcomes.
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Affiliation(s)
- Alexey A Tomskiy
- Department of Functional Neurosurgery, Burdenko National Medical Research Center of Neurosurgery, Moscow, Russian Federation.
| | - Anna A Poddubskaya
- Department of Functional Neurosurgery, Burdenko National Medical Research Center of Neurosurgery, Moscow, Russian Federation; Psychiatry Research Group, Burdenko National Medical Research Center of Neurosurgery, Moscow, Russian Federation
| | - Anna A Gamaleya
- Department of Functional Neurosurgery, Burdenko National Medical Research Center of Neurosurgery, Moscow, Russian Federation
| | - Oleg S Zaitsev
- Psychiatry Research Group, Burdenko National Medical Research Center of Neurosurgery, Moscow, Russian Federation
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19
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Kholyavin AI, Polyakov YI. Stereotactic cingulotomy and capsulotomy for obsessive-compulsive disorders: Indications and comparative results. PROGRESS IN BRAIN RESEARCH 2022; 272:1-21. [PMID: 35667796 DOI: 10.1016/bs.pbr.2022.03.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Stereotactic cingulotomy and capsulotomy have been used to treat obsessive-compulsive disorders (OCD) and treatment-resistant depression since the 1950s-60s. To date, these surgical procedures have gained a number of advancements due to progress of neuroimaging and upgrading of stereotactic technique. The effectiveness of operations is related to the restoration of the normal level of limbic regulation in treated patients. In cases of OCD, capsulotomy is somewhat more effective, while cingulotomy has a more favorable safety profile. Moreover, clinical experience shows that these procedures may be efficient for management not only OCD itself, but for obsessive-compulsive symptoms in cases of other mental diseases, such as Tourette syndrome and schizophrenia, thus may be considered in carefully selected patients. An individualized treatment strategy, including staged stereotactic interventions, seems most promising for attainment of the best possible outcomes, and may allow to achieve socialization of 75% of the operated patients with minimal pharmacological support. Other potential stereotactic targets for management of OCD, which selection may depend on detail of clinical manifestation of disease, include thalamic nuclei, nucleus accumbens, globus pallidus, the amygdala, etc., and are currently under active evaluation, and their use is tremendously facilitated by the development of deep brain stimulation techniques. Nevertheless, cingulotomy and capsulotomy still remain highly relevant for treatment of patients with therapy-resistant mental disorders.
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Affiliation(s)
- Andrey I Kholyavin
- Laboratory of Stereotactic Methods, N.P. Bechtereva Institute of Human Brain of the Russian Academy of Sciences, St. Petersburg, Russian Federation.
| | - Yury I Polyakov
- Laboratory of Stereotactic Methods, N.P. Bechtereva Institute of Human Brain of the Russian Academy of Sciences, St. Petersburg, Russian Federation; Department of Psychiatry and Narcology, I.I. Mechnikov North-Western State Medical University, St. Petersburg, Russian Federation; Department of Normal Physiology, I.P. Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russian Federation
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20
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Scaife JC, Eraifej J, Green AL, Petric B, Aziz TZ, Park RJ. Deep Brain Stimulation of the Nucleus Accumbens in Severe Enduring Anorexia Nervosa: A Pilot Study. Front Behav Neurosci 2022; 16:842184. [PMID: 35571282 PMCID: PMC9094709 DOI: 10.3389/fnbeh.2022.842184] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Accepted: 02/15/2022] [Indexed: 12/17/2022] Open
Abstract
Introduction Anorexia nervosa (AN) is one of the most debilitating psychiatric disorders, becoming severe and enduring in a third of cases; with few effective treatments. Deep brain stimulation is a reversible, adjustable neurosurgical procedure that has been gaining ground in psychiatry as a treatment for depression and obsessive-compulsive disorder, yet few studies have investigated AN. Abnormal eating behavior and the compulsive pursuit of thinness in AN is, in part, a consequence of dysfunction in reward circuitry and the nucleus accumbens (NAcc) is central to reward processing. Methods Phase 1 prospective open-label pilot study of seven individuals with severe enduring AN. Electrodes were implanted bilaterally into the NAcc with stimulation at the anterior limb of the internal capsule using rechargeable implantable pulse generators. The protocol of 15 months included 12 months of deep brain stimulation incorporating two consecutive, randomized blind on-off fortnights 9 months after stimulation onset. The primary objectives were to investigate safety and feasibility, together with changes in eating disorder psychopathology. Results Feasibility and safety was demonstrated with no serious adverse events due to deep brain stimulation. Three patients responded to treatment [defined as > 35% reduction in Eating Disorders Examination (EDE) score at 12 months] and four patients were non-responders. Responders had a statistically significant mean reduction in EDE scores (50.3% reduction; 95% CI 2.6-98.2%), Clinical Impairment Assessment (45.6% reduction; 95% CI 7.4-83.7%). Responders also had a statistically significant mean reduction in Hamilton Depression Scale, Hamilton Anxiety Scale and Snaith-Hamilton pleasure scale. There were no statistically significant changes in Body Mass Index, Yale-Brown-Cornell Eating Disorder Scale, Yale-Brown Obsessive-Compulsive Scale and World Health Organization Quality of Life Psychological subscale. Conclusion This study provides some preliminary indication that deep brain stimulation to the NAcc. Might potentially improve some key features of enduring AN. In this small study, the three responders had comorbid obsessive-compulsive disorder which predated AN diagnosis. Future studies should aim to further elucidate predictors of outcome. Clinical Trial Registration [www.ClinicalTrials.gov], identifier [Project ID 128658].
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Affiliation(s)
- Jessica C. Scaife
- Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, United Kingdom
- Oxford Health NHS Foundation Trust, Oxford, United Kingdom
- Nuffield Department of Surgical Sciences, John Radcliffe Hospital Oxford, University of Oxford, Oxford, United Kingdom
| | - John Eraifej
- Nuffield Department of Surgical Sciences, John Radcliffe Hospital Oxford, University of Oxford, Oxford, United Kingdom
- Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
| | - Alexander L. Green
- Nuffield Department of Surgical Sciences, John Radcliffe Hospital Oxford, University of Oxford, Oxford, United Kingdom
- Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
- Nuffield Department of Clinical Neuroscience, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
| | - Beth Petric
- Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
| | - Tipu Z. Aziz
- Nuffield Department of Surgical Sciences, John Radcliffe Hospital Oxford, University of Oxford, Oxford, United Kingdom
- Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
- Nuffield Department of Clinical Neuroscience, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
| | - Rebecca J. Park
- Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, United Kingdom
- Oxford Health NHS Foundation Trust, Oxford, United Kingdom
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21
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Kochanski RB, Slavin KV. The future perspectives of psychiatric neurosurgery. PROGRESS IN BRAIN RESEARCH 2022; 270:211-228. [PMID: 35396029 DOI: 10.1016/bs.pbr.2022.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
The future of psychiatric neurosurgery can be viewed from two separate perspectives: the immediate future and the distant future. Both show promise, but the treatment strategy for mental diseases and the technology utilized during these separate periods will likely differ dramatically. It can be expected that the initial advancements will be built upon progress of neuroimaging and stereotactic targeting while surgical technology becomes adapted to patient-specific symptomatology and structural/functional imaging parameters. This individualized approach has already begun to show significant promise when applied to deep brain stimulation for treatment-resistant depression and obsessive-compulsive disorder. If effectiveness of these strategies is confirmed by well designed, double-blind, placebo-controlled clinical studies, further technological advances will continue into the distant future, and will likely involve precise neuromodulation at the cellular level, perhaps using wireless technology with or without closed-loop design. This approach, being theoretically less invasive and carrying less risk, may ultimately propel psychiatric neurosurgery to the forefront in the treatment algorithm of mental illness. Despite prominent development of non-invasive therapeutic options, such as stereotactic radiosurgery or transcranial magnetic resonance-guided focused ultrasound, chances are there will still be a need in surgical management of patients with most intractable psychiatric conditions.
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Affiliation(s)
- Ryan B Kochanski
- Neurosurgery, Methodist Healthcare System, San Antonio, TX, United States
| | - Konstantin V Slavin
- Department of Neurosurgery, University of Illinois at Chicago, Chicago, IL, United States; Neurology Service, Jesse Brown Veterans Administration Medical Center, Chicago, IL, United States.
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22
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Messina G, Vetrano IG, Bonomo G, Broggi G. Role of deep brain stimulation in management of psychiatric disorders. PROGRESS IN BRAIN RESEARCH 2022; 270:61-96. [PMID: 35396031 DOI: 10.1016/bs.pbr.2022.01.026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Nowadays, most of patients affected by psychiatric disorders are successfully treated with conservative therapies. Still, a variable percentage of them demonstrate resistance to conventional treatments, and alternative methods can then be considered. During the last 20 years, there is a progressive interest in use of deep brain stimulation (DBS) in mental illnesses. It has become clear nowadays, that this modality may be effectively applied under specific indications in some patients with major depressive disorder, obsessive-compulsive disorder, anorexia nervosa and other eating disorders, Tourette syndrome, schizophrenia, substance use disorder, and even pathologically aggressive behavior. Despite the fact that the efficacy of neuromodulation with DBS, as well as of various lesional interventions, in cases of mental illnesses is still not fully established, there are several premises for wider applications of such "unclassical" psychiatric treatments in the future. Novel technologies of DBS, developments in non-invasive lesioning using stereotactic radiosurgery and transcranial magnetic resonance-guided focused ultrasound, and advances of neurophysiological and neuroimaging modalities may bolster further clinical applications of psychiatric neurosurgery, improve its results, and allow for individually selected treatment strategies tailored to specific needs of the patient.
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Affiliation(s)
- Giuseppe Messina
- Functional Neurosurgery Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
| | - Ignazio G Vetrano
- Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
| | - Giulio Bonomo
- Functional Neurosurgery Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
| | - Giovanni Broggi
- Functional Neurosurgery Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Department of Neurosurgery, M Cecilia Hospital-GVM, Ravenna, Italy
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23
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Germann J, Boutet A, Elias GJ, Gouveia FV, Loh A, Giacobbe P, Bhat V, Kucharczyk W, Lozano AM. Brain Structures and Networks Underlying Treatment Response to Deep Brain Stimulation Targeting the Inferior Thalamic Peduncle in Obsessive-Compulsive Disorder. Stereotact Funct Neurosurg 2022; 100:236-243. [DOI: 10.1159/000523826] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 02/23/2022] [Indexed: 12/17/2022]
Abstract
<b><i>Background:</i></b> Obsessive-compulsive disorder (OCD) is a debilitating disease with a lifetime prevalence of 2–3%. Neuromodulatory treatments have been successfully used in severe cases. Deep brain stimulation (DBS) targeting the inferior thalamic peduncle (ITP) has been shown to successfully alleviate symptoms in OCD patients; however, the brain circuits implicated remain unclear. Here, we investigate the efficacious neural substrates following ITP-DBS for OCD. <b><i>Methods:</i></b> High-quality normative structural and functional connectomics and voxel-wise probabilistic mapping techniques were applied to assess the neural substrates of OCD symptom alleviation in a cohort of 5 ITP-DBS patients. <b><i>Results:</i></b> The region of most efficacious stimulation was located in the regions of the ITP and bed nucleus of the stria terminalis. Both functional and structural connectomics analyses demonstrated that successful symptom alleviation involved a brain network encompassing the bilateral amygdala and prefrontal regions. <b><i>Limitations:</i></b> The main limitation is the small size of the ITP-DBS cohort. While the findings are highly consistent and significant, these should be validated in larger studies. <b><i>Conclusions:</i></b> These results identify a tripartite brain network – composed of the bilateral amygdala and prefrontal regions 24 and 46 – whose engagement is associated with greater symptom improvement. They also provide information for optimizing targeting and identifying network components critically involved in ITP-DBS treatment response. Amygdala engagement in particular seems to be a key component for clinical benefits and could constitute a biomarker for treatment optimization.
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Özek MM, Bozkurt B. Surgical Approach to Thalamic Tumors. Adv Tech Stand Neurosurg 2022; 45:177-198. [PMID: 35976450 DOI: 10.1007/978-3-030-99166-1_5] [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] [Indexed: 06/15/2023]
Abstract
Thalamic tumors are deep-seated lesions. Recent improvements in therapeutic approaches and surgical techniques have allowed a more accurate approach to these lesions and a reduction in morbidity and mortality. In this article, the various surgical approaches for the resection of thalamic tumors are described. Each of these approaches has its own indications and risk of complications. Resection of thalamic tumors needs specific anatomical knowledge, especially the vascular anatomy of the region and the thalamic peduncles.
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Affiliation(s)
- M Memet Özek
- Department of Neurosurgery, Division of Pediatric Neurosurgery, Acıbadem University, School of Medicine, Istanbul, Turkey.
| | - Baran Bozkurt
- Neuroanatomy Laboratory at Department of Neurosurgery, Acıbadem University, School of Medicine, Istanbul, Turkey
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25
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Rusche T, Kaufmann J, Voges J. Nucleus accumbens projections: Validity and reliability of fiber reconstructions based on high-resolution diffusion-weighted MRI. Hum Brain Mapp 2021; 42:5888-5910. [PMID: 34528323 PMCID: PMC8596959 DOI: 10.1002/hbm.25657] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 08/02/2021] [Accepted: 08/29/2021] [Indexed: 12/17/2022] Open
Abstract
Clinical effects of deep brain stimulation are largely mediated by the activation of myelinated axons. Hence, increasing attention has been paid in the past on targeting white matter tracts in addition to gray matter. Aims of the present study were: (i) visualization of discrete afferences and efferences of the nucleus accumbens (NAc), supposed to be a major hub of neural networks relating to mental disorders, using probabilistic fiber tractography and a data driven approach, and (ii) validation of the applied methodology for standardized routine clinical applications. MR‐data from 11 healthy subjects and 7 measurement sessions each were acquired on a 3T MRI‐scanner. For probabilistic fiber tracking the NAc as a seed region and the medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), amygdala (AMY), hippocampus (HPC), dorsomedial thalamus (dmT) and ventral tegmental area (VTA) as target regions were segmented for each subject and both hemispheres. To quantitatively assess the reliability and stability of the reconstructions, we filtered and clustered the individual fiber‐tracts (NAc to target) for each session and subject and performed a point‐by‐point calculation of the maximum cluster distances for intra‐subject comparison. The connectivity patterns formed by the obtained fibers were in good concordance with published data from tracer and/or fiber‐dissection studies. Furthermore, the reliability assessment of the (NAc to target)‐fiber‐tracts yielded to high correlations between the obtained clustered‐tracts. Using DBS with directional lead technology, the workflow elaborated in this study may guide selective electrical stimulation of NAc projections.
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Affiliation(s)
- Thilo Rusche
- Department of Stereotactic Neurosurgery, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.,Department of Radiology, Clinic of Radiology & Nuclear Medicine, University Hospital Basel, University Basel, Basel, Switzerland
| | - Jörn Kaufmann
- Department of Neurology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - Jürgen Voges
- Department of Stereotactic Neurosurgery, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
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Welter ML, Alves Dos Santos JF, Clair AH, Lau B, Diallo HM, Fernandez-Vidal S, Belaid H, Pelissolo A, Domenech P, Karachi C, Mallet L. Deep Brain Stimulation of the Subthalamic, Accumbens, or Caudate Nuclei for Patients With Severe Obsessive-Compulsive Disorder: A Randomized Crossover Controlled Study. Biol Psychiatry 2021; 90:e45-e47. [PMID: 33012521 DOI: 10.1016/j.biopsych.2020.07.013] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 07/20/2020] [Accepted: 07/21/2020] [Indexed: 12/13/2022]
Affiliation(s)
- Marie-Laure Welter
- Institut du cerveau et de la moelle épinière, French Institute of Health and Medical Research U1127, French National Centre for Scientific Research Joint Research Unit 7225, Sorbonne Université, Paris, France; Neurophysiology Department, Clinical Research Center-Biological Resources Center 1404, Centre Hospitalier Universitaire de Rouen, University of Rouen, Rouen, France
| | | | - Anne-Helene Clair
- Institut du cerveau et de la moelle épinière, French Institute of Health and Medical Research U1127, French National Centre for Scientific Research Joint Research Unit 7225, Sorbonne Université, Paris, France
| | - Brian Lau
- Institut du cerveau et de la moelle épinière, French Institute of Health and Medical Research U1127, French National Centre for Scientific Research Joint Research Unit 7225, Sorbonne Université, Paris, France
| | - Hassimiou Mamadou Diallo
- Institut Pierre Louis d'Epidémiologie et de Santé Publique, French Institute of Health and Medical Research, Paris, France
| | - Sara Fernandez-Vidal
- Institut du cerveau et de la moelle épinière, French Institute of Health and Medical Research U1127, French National Centre for Scientific Research Joint Research Unit 7225, Sorbonne Université, Paris, France
| | - Hayat Belaid
- Neurosurgery Department, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Antoine Pelissolo
- French Institute of Health and Medical Research U955, Mondor Institute for Biomedical Research, Créteil, France; Neurosurgery Department, Département Médico-Universitaire de psychiatrie et d'addictologie, Hôpitaux Universitaires Henri Mondor - Albert Chenevier, Assistance Publique-Hôpitaux de Paris, Université Paris-Est Créteil, Créteil, France
| | - Philippe Domenech
- Institut du cerveau et de la moelle épinière, French Institute of Health and Medical Research U1127, French National Centre for Scientific Research Joint Research Unit 7225, Sorbonne Université, Paris, France; Neurosurgery Department, Département Médico-Universitaire de psychiatrie et d'addictologie, Hôpitaux Universitaires Henri Mondor - Albert Chenevier, Assistance Publique-Hôpitaux de Paris, Université Paris-Est Créteil, Créteil, France
| | - Carine Karachi
- Institut du cerveau et de la moelle épinière, French Institute of Health and Medical Research U1127, French National Centre for Scientific Research Joint Research Unit 7225, Sorbonne Université, Paris, France; Neurosurgery Department, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Luc Mallet
- Institut du cerveau et de la moelle épinière, French Institute of Health and Medical Research U1127, French National Centre for Scientific Research Joint Research Unit 7225, Sorbonne Université, Paris, France; Neurosurgery Department, Département Médico-Universitaire de psychiatrie et d'addictologie, Hôpitaux Universitaires Henri Mondor - Albert Chenevier, Assistance Publique-Hôpitaux de Paris, Université Paris-Est Créteil, Créteil, France; Department of Mental Health and Psychiatry, Global Health Institute, University of Geneva, Geneva, Switzerland.
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27
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Decreased left amygdala functional connectivity by cognitive-coping therapy in obsessive-compulsive disorder. Mol Psychiatry 2021; 26:6952-6962. [PMID: 33963282 DOI: 10.1038/s41380-021-01131-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 04/01/2021] [Accepted: 04/14/2021] [Indexed: 12/17/2022]
Abstract
It is of great clinical importance to explore more efficacious treatments for OCD. Recently, cognitive-coping therapy (CCT), mainly focusing on recognizing and coping with a fear of negative events, has been reported as an efficacious psychotherapy. However, the underlying neurophysiological mechanism remains unknown. This study of 79 OCD patients collected Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and resting-state functional magnetic resonance imaging (rs-fMRI) scans before and after four weeks of CCT, pharmacotherapy plus CCT (pCCT), or pharmacotherapy. Amygdala seed-based functional connectivity (FC) analysis was performed. Compared post- to pretreatment, pCCT-treated patients showed decreased left amygdala (LA) FC with the right anterior cingulate gyrus (cluster 1) and with the left paracentral lobule/the parietal lobe (cluster 2), while CCT-treated patients showed decreased LA-FC with the left middle occipital gyrus/the left superior parietal/left inferior parietal (cluster 3). The z-values of LA-FC with the three clusters were significantly lower after pCCT or CCT than pretreatment in comparisons of covert vs. overt and of non-remission vs. remission patients, except the z-value of cluster 2 in covert OCD. CCT and pCCT significantly reduced the Y-BOCS score. The reduction in the Y-BOCS score was positively correlated with the z-value of cluster 1. Our findings demonstrate that both pCCT and CCT with large effect sizes lowered LA-FC, indicating that FCs were involved in OCD. Additionally, decreased LA-FC with the anterior cingulate cortex (ACC) or paracentral/parietal cortex may be a marker for pCCT response or a marker for distinguishing OCD subtypes. Decreased LA-FC with the parietal region may be a common pathway of pCCT and CCT. Trial registration: ChiCTR-IPC-15005969.
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28
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Shi L, Fan S, Yuan T, Fang H, Zheng J, Xiao Z, Diao Y, Zhu G, Zhang Q, Liu H, Zhang H, Meng F, Zhang J, Yang A. Microstimulation Is a Promising Approach in Achieving Better Lead Placement in Subthalamic Nucleus Deep Brain Stimulation Surgery. Front Neurol 2021; 12:683532. [PMID: 34630273 PMCID: PMC8493285 DOI: 10.3389/fneur.2021.683532] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Accepted: 08/16/2021] [Indexed: 11/24/2022] Open
Abstract
Background: The successful application of subthalamic nucleus (STN) deep brain stimulation (DBS) surgery relies mostly on optimal lead placement, whereas the major challenge is how to precisely localize STN. Microstimulation, which can induce differentiating inhibitory responses between STN and substantia nigra pars reticulata (SNr) near the ventral border of STN, has indicated a great potential of breaking through this barrier. Objective: This study aims to investigate the feasibility of localizing the boundary between STN and SNr (SSB) using microstimulation and promote better lead placement. Methods: We recorded neurophysiological data from 41 patients undergoing STN-DBS surgery with microstimulation in our hospital. Trajectories with typical STN signal were included. Microstimulation was applied near the bottom of STN to determine SSB, which was validated by the imaging reconstruction of DBS leads. Results: In most trajectories with microstimulation (84.4%), neuronal firing in STN could not be inhibited by microstimulation, whereas in SNr long inhibition was observed following microstimulation. The success rate of localizing SSB was significantly higher in trajectories with microstimulation than those without. Moreover, results from imaging reconstruction and intraoperative neurological assessments demonstrated better lead location and higher therapeutic effectiveness in trajectories with microstimulation and accurately identified SSB. Conclusion: Microstimulation on microelectrode recording is an effective approach to localize the SSB. Our data provide clinical evidence that microstimulation can be routinely employed to achieve better lead placement.
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Affiliation(s)
- Lin Shi
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Beijing, China
| | - Shiying Fan
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Tianshuo Yuan
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Huaying Fang
- Beijing Advanced Innovation Center for Imaging Theory and Technology, Capital Normal University, Beijing, China
- Academy for Multidisciplinary Studies, Capital Normal University, Beijing, China
| | - Jie Zheng
- Department of Ophthalmology, Children's Hospital, Harvard Medical School, Boston, MA, United States
| | - Zunyu Xiao
- Molecular Imaging Research Center, Harbin Medical University, Harbin, China
| | - Yu Diao
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Guanyu Zhu
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Quan Zhang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Huanguang Liu
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Hua Zhang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Fangang Meng
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Beijing, China
| | - Jianguo Zhang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Beijing, China
| | - Anchao Yang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Beijing, China
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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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30
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Komaitis S, Koutsarnakis C, Lani E, Kalamatianos T, Drosos E, Skandalakis GP, Liakos F, Liouta E, Kalyvas AV, Stranjalis G. Deciphering the frontostriatal circuitry through the fiber dissection technique: direct structural evidence on the morphology and axonal connectivity of the fronto-caudate tract. J Neurosurg 2021; 135:815-827. [PMID: 33385993 DOI: 10.3171/2020.7.jns201287] [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: 04/16/2020] [Accepted: 07/13/2020] [Indexed: 11/06/2022]
Abstract
OBJECTIVE The authors sought to investigate the very existence and map the topography, morphology, and axonal connectivity of a thus far ill-defined subcortical pathway known as the fronto-caudate tract (FCT) since there is a paucity of direct structural evidence regarding this pathway in the relevant literature. METHODS Twenty normal adult cadaveric formalin-fixed cerebral hemispheres (10 left and 10 right) were explored through the fiber microdissection technique. Lateral to medial and medial to lateral dissections were carried out in a tandem manner in all hemispheres. Attention was focused on the prefrontal area and central core since previous diffusion tensor imaging studies have recorded the tract to reside in this territory. RESULTS In all cases, the authors readily identified the FCT as a fan-shaped pathway lying in the most medial layer of the corona radiata and traveling across the subependymal plane before terminating on the superolateral margin of the head and anterior part of the body of the caudate nucleus. The FCT could be adequately differentiated from adjacent fiber tracts and was consistently recorded to terminate in Brodmann areas 8, 9, 10, and 11 (anterior pre-supplementary motor area and the dorsolateral, frontopolar, and fronto-orbital prefrontal cortices). The authors were also able to divide the tract into a ventral and a dorsal segment according to the respective topography and connectivity observed. Hemispheric asymmetries were not observed, but instead the authors disclosed asymmetry within the FCT, with the ventral segment always being thicker and bulkier than the dorsal one. CONCLUSIONS By using the fiber microdissection technique, the authors provide sound structural evidence on the topography, morphology, and connectional anatomy of the FCT as a distinct part of a wider frontostriatal circuitry. The findings are in line with the tract's putative functional implications in high-order motor and behavioral processes and can potentially inform current surgical practice in the fields of neuro-oncology and functional neurosurgery.
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Affiliation(s)
- Spyridon Komaitis
- 1Athens Microneurosurgery Laboratory, Evangelismos Hospital, Athens
- 2Department of Neurosurgery, Evangelismos Hospital, National and Kapodistrian University of Athens, Greece
- 4Department of Anatomy, Medical School, National and Kapodistrian University of Athens
- 5Hellenic Center for Neurosurgical Research, "Petros Kokkalis," Athens, Greece
| | - Christos Koutsarnakis
- 1Athens Microneurosurgery Laboratory, Evangelismos Hospital, Athens
- 2Department of Neurosurgery, Evangelismos Hospital, National and Kapodistrian University of Athens, Greece
- 4Department of Anatomy, Medical School, National and Kapodistrian University of Athens
- 5Hellenic Center for Neurosurgical Research, "Petros Kokkalis," Athens, Greece
| | - Evgenia Lani
- 1Athens Microneurosurgery Laboratory, Evangelismos Hospital, Athens
- 4Department of Anatomy, Medical School, National and Kapodistrian University of Athens
| | - Theodosis Kalamatianos
- 1Athens Microneurosurgery Laboratory, Evangelismos Hospital, Athens
- 5Hellenic Center for Neurosurgical Research, "Petros Kokkalis," Athens, Greece
| | - Evangelos Drosos
- 1Athens Microneurosurgery Laboratory, Evangelismos Hospital, Athens
- 2Department of Neurosurgery, Evangelismos Hospital, National and Kapodistrian University of Athens, Greece
- 5Hellenic Center for Neurosurgical Research, "Petros Kokkalis," Athens, Greece
| | - Georgios P Skandalakis
- 1Athens Microneurosurgery Laboratory, Evangelismos Hospital, Athens
- 4Department of Anatomy, Medical School, National and Kapodistrian University of Athens
- 7Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Faidon Liakos
- 1Athens Microneurosurgery Laboratory, Evangelismos Hospital, Athens
- 4Department of Anatomy, Medical School, National and Kapodistrian University of Athens
| | - Evangelia Liouta
- 1Athens Microneurosurgery Laboratory, Evangelismos Hospital, Athens
- 5Hellenic Center for Neurosurgical Research, "Petros Kokkalis," Athens, Greece
| | - Aristotelis V Kalyvas
- 1Athens Microneurosurgery Laboratory, Evangelismos Hospital, Athens
- 4Department of Anatomy, Medical School, National and Kapodistrian University of Athens
- 6Division of Neurosurgery, Toronto Western Hospital, University Health Network, University of Toronto, Ontario, Canada; and
| | - George Stranjalis
- 1Athens Microneurosurgery Laboratory, Evangelismos Hospital, Athens
- 2Department of Neurosurgery, Evangelismos Hospital, National and Kapodistrian University of Athens, Greece
- 4Department of Anatomy, Medical School, National and Kapodistrian University of Athens
- 5Hellenic Center for Neurosurgical Research, "Petros Kokkalis," Athens, Greece
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31
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Liu W, Shao H, Liao J, Yang D, Ma M, Yang J. Continuous Theta-Burst Stimulation Over the Right Orbitofrontal Cortex in Treatment-Resistant Obsessive-Compulsive Disorder Treatment: A Randomized Sham-Controlled Trial. Int J Gen Med 2021; 14:3109-3118. [PMID: 34234539 PMCID: PMC8257072 DOI: 10.2147/ijgm.s318069] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Accepted: 06/17/2021] [Indexed: 12/15/2022] Open
Abstract
Purpose Examining whether modulation of right orbitofrontal cortex (OFC) activity by continuous theta-burst stimulation (cTBS) affects obsessive-compulsive disorder (OCD) symptoms. Patients and Methods A total of 28 treatment-resistant OCD participants were treated with either active or sham cTBS of the OFC twice per day, for five days a week, for 2 weeks, in a double-blinded manner. Clinical response to treatment was determined using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Results There were no statistically significant differences between the 2 groups after two weeks of treatment in the Yale-Brown Obsessive-Compulsive Scale score (group*time interaction, F2,20=0.996, p=0.387) and other secondary outcome measures, including anxiety symptoms and responder rates. Depressive symptoms improved significantly in the active group (p=0.027), but the significant difference disappeared at 6 weeks (p=0.089). Conclusion This is the first randomized controlled study using cTBS in the right OFC to observe the improvement of treatment-resistant OCD symptoms. It is safe to use cTBS, but 2 weeks of treatment is not enough to achieve a curative effect. Future studies are needed to explore more advanced stimulation parameters suitable for the treatment of OCD. Clinical Trial Registration www.chictr.org.cn, identifier ChiCTR2000034814.
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Affiliation(s)
- Weiwei Liu
- Tianjin Medical University, Tianjin, People's Republic of China
| | - Hua Shao
- Clinical Psychology Department, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Jing Liao
- Tianjin Medical University, Tianjin, People's Republic of China
| | - Dalu Yang
- Tianjin Medical University, Tianjin, People's Republic of China
| | - Maoliang Ma
- Tianjin Medical University General Hospital Airport Site, Tianjin, People's Republic of China
| | - Jianli Yang
- Clinical Psychology Department, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
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32
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Arumugham SS, Srinivas D, Narayanaswamy JC, Jaisoorya TS, Kashyap H, Domenech P, Palfi S, Mallet L, Venkatasubramanian G, Reddy YJ. Identification of biomarkers that predict response to subthalamic nucleus deep brain stimulation in resistant obsessive-compulsive disorder: protocol for an open-label follow-up study. BMJ Open 2021; 11:e047492. [PMID: 34158304 PMCID: PMC8220486 DOI: 10.1136/bmjopen-2020-047492] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 05/26/2021] [Indexed: 11/04/2022] Open
Abstract
INTRODUCTION Deep brain stimulation (DBS) of bilateral anteromedial subthalamic nucleus (amSTN) has been found to be helpful in a subset of patients with severe, chronic and treatment-refractory obsessive-compulsive disorder (OCD). Biomarkers may aid in patient selection and optimisation of this invasive treatment. In this trial, we intend to evaluate neurocognitive function related to STN and related biosignatures as potential biomarkers for STN DBS in OCD. METHODS AND ANALYSIS Twenty-four subjects with treatment-refractory OCD will undergo open-label STN DBS. Structural/functional imaging, electrophysiological recording and neurocognitive assessment would be performed at baseline. The subjects would undergo a structured clinical assessment for 12 months postsurgery. A group of 24 healthy volunteers and 24 subjects with treatment-refractory OCD who receive treatment as usual would be recruited for comparison of biomarkers and treatment response, respectively. Baseline biomarkers would be evaluated as predictors of clinical response. Neuroadaptive changes would be studied through a reassessment of neurocognitive functioning, imaging and electrophysiological activity post DBS. ETHICS AND DISSEMINATION The protocol has been approved by the National Institute of Mental Health and Neurosciences Ethics Committee. The study findings will be disseminated through peer-reviewed scientific journals and scientific meetings.
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Affiliation(s)
- Shyam Sundar Arumugham
- Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
| | - Dwarakanath Srinivas
- Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
| | - Janardhanan C Narayanaswamy
- Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
| | - T S Jaisoorya
- Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
| | - Himani Kashyap
- Department of Clinical Psychology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
| | - Philippe Domenech
- Univ Paris-Est Créteil, DMU CARE - Département Médical-Universitaire de Chirurgie et Anesthésie réanimation, DMU IMPACT, Département Médical-Universitaire de Psychiatrie et d'Addictologie, Hôpitaux Universitaires Henri Mondor, Creteil, France
- Univ of Paris 12 UPEC, Faculté de médecine, INSERM U955, Creteil, France
| | - Stéphane Palfi
- Univ Paris-Est Créteil, DMU CARE - Département Médical-Universitaire de Chirurgie et Anesthésie réanimation, DMU IMPACT, Département Médical-Universitaire de Psychiatrie et d'Addictologie, Hôpitaux Universitaires Henri Mondor, Creteil, France
- Univ of Paris 12 UPEC, Faculté de médecine, INSERM U955, Creteil, France
| | - Luc Mallet
- Institut du Cerveau, ICM, Inserm U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France
- Department of Mental Health and Psychiatry, University of Geneva, Geneva, Switzerland
| | - Ganesan Venkatasubramanian
- Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
| | - Yc Janardhan Reddy
- Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
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Mahoney JJ, Haut MW, Hodder SL, Zheng W, Lander LR, Berry JH, Farmer DL, Marton JL, Ranjan M, Brandmeir NJ, Finomore VS, Hensley JL, Aklin WM, Wang GJ, Tomasi D, Shokri-Kojori E, Rezai AR. Deep brain stimulation of the nucleus accumbens/ventral capsule for severe and intractable opioid and benzodiazepine use disorder. Exp Clin Psychopharmacol 2021; 29:210-215. [PMID: 34043402 PMCID: PMC8422285 DOI: 10.1037/pha0000453] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Given high relapse rates and the prevalence of overdose deaths, novel treatments for substance use disorder (SUD) are desperately needed for those who are treatment refractory. The objective of this study was to evaluate the safety of deep brain stimulation (DBS) for SUD and the effects of DBS on substance use, substance craving, emotional symptoms, and frontal/executive functions. DBS electrodes were implanted bilaterally within the Nucleus Accumbens/Ventral anterior internal capsule (NAc/VC) of a man in his early 30s with >10-year history of severe treatment refractory opioid and benzodiazepine use disorders. DBS of the NAc/VC was found to be safe with no serious adverse events noted and the participant remained abstinent and engaged in comprehensive treatment at the 12-week endpoint (and 12-month extended follow-up). Using a 0-100 visual analog scale, substance cravings decreased post-DBS implantation; most substantially in benzodiazepine craving following the final DBS titration (1.0 ± 2.2) compared to baseline (53.4 ± 29.5; p < .001). A trend toward improvement in frontal/executive function was observed on the balloon analog risk task performance following the final titration (217.7 ± 76.2) compared to baseline (131.3 ± 28.1, p = .066). FDG PET demonstrated an increase in glucose metabolism in the dorsolateral prefrontal and medial premotor cortices at the 12-week endpoint compared to post-surgery/pre-DBS titration. Heart Rate Variability (HRV) improved following the final titration (rMSSD = 56.0 ± 11.7) compared to baseline (19.2 ± 8.2; p < .001). In a participant with severe, treatment refractory opioid and benzodiazepine use disorder, DBS of the NAc/VC was safe, reduced substance use and craving, and improved frontal and executive functions. Confirmation of these findings with future studies is needed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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Affiliation(s)
- James J. Mahoney
- Department of Behavioral Medicine and Psychiatry, Department of Neuroscience, Rockefeller Neuroscience Institute (RNI), West Virginia University School of Medicine (WVUSOM)
| | - Marc W. Haut
- Department of Behavioral Medicine and Psychiatry, Department of Neuroscience, Rockefeller Neuroscience Institute (RNI), West Virginia University School of Medicine (WVUSOM),Department of Neurology, Department of Radiology, RNI, WVUSOM
| | - Sally L. Hodder
- West Virginia Clinical and Translational Science Institute, WVUSOM
| | - Wanhong Zheng
- Department of Behavioral Medicine and Psychiatry, Department of Neuroscience, Rockefeller Neuroscience Institute (RNI), West Virginia University School of Medicine (WVUSOM)
| | - Laura R. Lander
- Department of Behavioral Medicine and Psychiatry, Department of Neuroscience, Rockefeller Neuroscience Institute (RNI), West Virginia University School of Medicine (WVUSOM)
| | - James H. Berry
- Department of Behavioral Medicine and Psychiatry, Department of Neuroscience, Rockefeller Neuroscience Institute (RNI), West Virginia University School of Medicine (WVUSOM)
| | - Daniel L. Farmer
- Department of Behavioral Medicine and Psychiatry, Department of Neuroscience, Rockefeller Neuroscience Institute (RNI), West Virginia University School of Medicine (WVUSOM)
| | - Jennifer L. Marton
- Department of Behavioral Medicine and Psychiatry, Department of Neuroscience, Rockefeller Neuroscience Institute (RNI), West Virginia University School of Medicine (WVUSOM)
| | - Manish Ranjan
- Department of Neurosurgery, Department of Neuroscience, RNI, WVUSOM
| | | | | | | | - Will M. Aklin
- National Institutes of Health, National Institute on Drug Abuse, Bethesda, Maryland, United States
| | - Gene-Jack Wang
- National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, United States
| | - Dardo Tomasi
- National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, United States
| | - Ehsan Shokri-Kojori
- National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, United States
| | - Ali R. Rezai
- Department of Neurosurgery, Department of Neuroscience, RNI, WVUSOM
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Paulo DL, Bick SK. Advanced Imaging in Psychiatric Neurosurgery: Toward Personalized Treatment. Neuromodulation 2021; 25:195-201. [PMID: 33788971 DOI: 10.1111/ner.13392] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 02/22/2021] [Accepted: 03/08/2021] [Indexed: 11/30/2022]
Abstract
OBJECTIVES Our aim is to review several recent landmark studies discussing the application of advanced neuroimaging to guide target selection in deep brain stimulation (DBS) for psychiatric disorders. MATERIALS AND METHODS We performed a PubMed literature search of articles related to psychiatric neurosurgery, DBS, diffusion tensor imaging, probabilistic tractography, functional magnetic resonance imaging (MRI), and blood oxygen level-dependent activation. Relevant articles were included in the review. RESULTS Recent advances in neuroimaging, namely the use of diffusion tensor imaging, probabilistic tractography, functional MRI, and Positron emission tomography have provided higher resolution depictions of structural and functional connectivity between regions of interest. Applying these imaging modalities to DBS has increased understanding of the mechanism of action of DBS from the single structure to network level, allowed for new DBS targets to be discovered, and allowed for individualized DBS targeting for psychiatric indications. CONCLUSIONS Advanced neuroimaging techniques may be especially important to guide personalized DBS targeting in psychiatric disorders such as treatment-resistant depression and obsessive-compulsive disorder where symptom profiles and underlying disordered circuitry are more heterogeneous. These articles suggest that advanced imaging can help to further individualize and optimize DBS, a promising next step in improving its efficacy.
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Affiliation(s)
- Danika L Paulo
- Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Sarah K Bick
- Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
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Alternatives to Pharmacological and Psychotherapeutic Treatments in Psychiatric Disorders. PSYCHIATRY INTERNATIONAL 2021. [DOI: 10.3390/psychiatryint2010001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Nowadays, most of the patients affected by psychiatric disorders are successfully treated with psychotherapy and pharmacotherapy. Nevertheless, according to the disease, a variable percentage of patients results resistant to such modalities, and alternative methods can then be considered. The purpose of this review is to summarize the techniques and results of invasive modalities for several treatment-resistant psychiatric diseases. A literature search was performed to provide an up-to-date review of advantages, disadvantages, efficacy, and complications of Deep-Brain Stimulation, Magnetic Resonance-guided Focused-Ultrasound, radiofrequency, and radiotherapy lesioning for depression, obsessive-compulsive disorder, schizophrenia, addiction, anorexia nervosa, and Tourette’s syndrome. The literature search did not strictly follow the criteria for a systematic review: due to the large differences in methodologies and patients’ cohort, we tried to identify the highest quality of available evidence for each technique. We present the data as a comprehensive, narrative review about the role, indication, safety, and results of the contemporary instrumental techniques that opened new therapeutic fields for selected patients unresponsive to psychotherapy and pharmacotherapy.
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Abstract
It becomes increasingly clear that (non-)invasive neurostimulation is an effective treatment for obsessive-compulsive disorder (OCD). In this chapter we review the available evidence on techniques and targets, clinical results including a meta-analysis, mechanisms of action, and animal research. We focus on deep brain stimulation (DBS), but also cover non-invasive neurostimulation including transcranial magnetic stimulation (TMS). Data shows that most DBS studies target the ventral capsule/ventral striatum (VC/VS), with an overall 76% response rate in treatment-refractory OCD. Also TMS holds clinical promise. Increased insight in the normalizing effects of neurostimulation on cortico-striatal-thalamic-cortical (CSTC) loops - through neuroimaging and animal research - provides novel opportunities to further optimize treatment strategies. Advancing clinical implementation of neurostimulation techniques is essential to ameliorate the lives of the many treatment-refractory OCD patients.
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Ota M, Kanie A, Kobayashi Y, Nakajima A, Sato N, Horikoshi M. Pseudo-continuous arterial spin labeling MRI study of patients with obsessive-compulsive disorder. Psychiatry Res Neuroimaging 2020; 303:111124. [PMID: 32563075 DOI: 10.1016/j.pscychresns.2020.111124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Revised: 05/18/2020] [Accepted: 06/11/2020] [Indexed: 10/24/2022]
Abstract
Arterial spin labeling (ASL) magnetic resonance imaging is a novel technique that can measure regional cerebral blood flow (rCBF). Here we used pseudo-continuous ASL (pCASL) to examine the structural and functional imaging data in patients with obsessive-compulsive disorder (OCD). We estimated the gray matter volume imaging and pCASL imaging data by means of a voxel-by-voxel statistical analysis. We evaluated the differences of rCBF and gray matter volume between the OCD patients and healthy subjects. We detected a significant rCBF reduction in OCD patients in the right posterior cingulate extending to the lingual gyrus, thalamus, and hippocampus, and a significant increase in the left temporal gyrus and left frontal white matter region, compared with healthy subjects. We also observed a significant reduction in gray matter volume of OCD patients in the right hippocampus. We also estimated the correlation between the clinical severity of OCD and the rCBF and gray matter volumes, and found significant negative correlations between the severity of illness and the regional gray matter volume in the bilateral anterior cingulate corti. Our study demonstrated significant changes of rCBF in the cortico-striato-thalamo-cortical pathway around the hippocampus in OCD patients. These findings may help to elucidate the pathogenesis of OCD.
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Affiliation(s)
- Miho Ota
- Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Department of Neuropsychiatry, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8576, Japan.
| | - Ayako Kanie
- National Center for Cognitive Behavior Therapy and Research, National Center of Neurology and Psychiatry, 4-1-1, Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan
| | - Yuki Kobayashi
- National Center for Cognitive Behavior Therapy and Research, National Center of Neurology and Psychiatry, 4-1-1, Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan
| | - Aiichiro Nakajima
- National Center for Cognitive Behavior Therapy and Research, National Center of Neurology and Psychiatry, 4-1-1, Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan
| | - Noriko Sato
- Department of Radiology, National Center of Neurology and Psychiatry, 4-1-1, Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan
| | - Masaru Horikoshi
- National Center for Cognitive Behavior Therapy and Research, National Center of Neurology and Psychiatry, 4-1-1, Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan
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Bronte-Stewart HM, Petrucci MN, O’Day JJ, Afzal MF, Parker JE, Kehnemouyi YM, Wilkins KB, Orthlieb GC, Hoffman SL. Perspective: Evolution of Control Variables and Policies for Closed-Loop Deep Brain Stimulation for Parkinson's Disease Using Bidirectional Deep-Brain-Computer Interfaces. Front Hum Neurosci 2020; 14:353. [PMID: 33061899 PMCID: PMC7489234 DOI: 10.3389/fnhum.2020.00353] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 08/05/2020] [Indexed: 11/21/2022] Open
Abstract
A deep brain stimulation system capable of closed-loop neuromodulation is a type of bidirectional deep brain-computer interface (dBCI), in which neural signals are recorded, decoded, and then used as the input commands for neuromodulation at the same site in the brain. The challenge in assuring successful implementation of bidirectional dBCIs in Parkinson's disease (PD) is to discover and decode stable, robust and reliable neural inputs that can be tracked during stimulation, and to optimize neurostimulation patterns and parameters (control policies) for motor behaviors at the brain interface, which are customized to the individual. In this perspective, we will outline the work done in our lab regarding the evolution of the discovery of neural and behavioral control variables relevant to PD, the development of a novel personalized dual-threshold control policy relevant to the individual's therapeutic window and the application of these to investigations of closed-loop STN DBS driven by neural or kinematic inputs, using the first generation of bidirectional dBCIs.
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Affiliation(s)
- Helen M. Bronte-Stewart
- Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States
- Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, United States
| | - Matthew N. Petrucci
- Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States
| | - Johanna J. O’Day
- Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States
- Department of Bioengineering, Stanford University, Stanford, CA, United States
| | - Muhammad Furqan Afzal
- Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States
- Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Jordan E. Parker
- Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States
| | - Yasmine M. Kehnemouyi
- Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States
| | - Kevin B. Wilkins
- Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States
| | - Gerrit C. Orthlieb
- Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States
| | - Shannon L. Hoffman
- Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States
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Emotions Modulate Subthalamic Nucleus Activity: New Evidence in Obsessive-Compulsive Disorder and Parkinson's Disease Patients. BIOLOGICAL PSYCHIATRY: COGNITIVE NEUROSCIENCE AND NEUROIMAGING 2020; 6:556-567. [PMID: 33060034 DOI: 10.1016/j.bpsc.2020.08.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 08/05/2020] [Accepted: 08/06/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Subthalamic nucleus (STN) deep brain stimulation alleviates obsessive-compulsive disorder (OCD) symptoms, suggesting that this basal ganglia structure may play a key role in integrating limbic and motor information. We explored the modulation of STN neural activity by visual emotional information under different motor demands. METHODS We compared STN local field potentials acquired in 7 patients with OCD and 15 patients with Parkinson's disease off and on levodopa while patients categorized pictures as unpleasant, pleasant, or neutral and pressed a button for 1 of these 3 categories depending on the instruction. RESULTS During image presentation, theta power increased for unpleasant compared with neutral images in both patients with OCD and patients with Parkinson's disease. Only in patients with OCD was theta power also increased in pleasant compared with neutral trials. During the button press in patients with OCD, no modification of STN activity was seen on average, but theta power increased when the image triggering the motor response was unpleasant. Conversely, in patients with Parkinson's disease, a beta decrease was observed during the button press unrelated to the valence of the stimulus. Finally, in patients with OCD, a significant positive relationship was observed between the amplitude of the emotionally related theta response and symptom severity (measured using the Yale-Brown Obsessive Compulsive Scale). CONCLUSIONS We highlighted modulations of STN theta band activity related to emotions that were specific to OCD and correlated with OCD symptom severity. STN theta-induced activity might therefore underlie dysfunction of the limbic STN and its related network leading to OCD pathophysiology.
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Spatio-molecular domains identified in the mouse subthalamic nucleus and neighboring glutamatergic and GABAergic brain structures. Commun Biol 2020; 3:338. [PMID: 32620779 PMCID: PMC7334224 DOI: 10.1038/s42003-020-1028-8] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 05/20/2020] [Indexed: 01/07/2023] Open
Abstract
The subthalamic nucleus (STN) is crucial for normal motor, limbic and associative function. STN dysregulation is correlated with several brain disorders, including Parkinsonʼs disease and obsessive compulsive disorder (OCD), for which high-frequency stimulation of the STN is increasing as therapy. However, clinical progress is hampered by poor knowledge of the anatomical–functional organization of the STN. Today, experimental mouse genetics provides outstanding capacity for functional decoding, provided selective promoters are available. Here, we implemented single-nuclei RNA sequencing (snRNASeq) of the mouse STN followed through with histological analysis of 16 candidate genes of interest. Our results demonstrate that the mouse STN is composed of at least four spatio-molecularly defined domains, each distinguished by defined sets of promoter activities. Further, molecular profiles dissociate the STN from the adjoining para-STN (PSTN) and neighboring structures of the hypothalamus, mammillary nuclei and zona incerta. Enhanced knowledge of STN´s internal organization should prove useful towards genetics-based functional decoding of this clinically relevant brain structure. Wallén-Mackenzie et al. investigate anatomical–functional organization of the subthalamic nucleus in mice, using single-nuclei RNA sequencing followed by histological analysis. They identify four domains distinguished by defined sets of promoter activities, providing a valuable resource for functional decoding of the subthalamic nucleus.
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