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Dong J, Dai M, Guo Z, Xu T, Li F, Li J. The Targets of Deep Brain Stimulation in the Treatment of Treatment-Resistant Depression: A Review. Brain Behav 2025; 15:e70505. [PMID: 40321033 PMCID: PMC12050660 DOI: 10.1002/brb3.70505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 03/24/2025] [Accepted: 04/09/2025] [Indexed: 05/08/2025] Open
Abstract
PURPOSE The purpose of this review is to evaluate the current state and potential future directions of deep brain stimulation (DBS) therapy for treatment-resistant depression (TRD), a condition that significantly impacts patients' quality of life and for which conventional treatments are often ineffective. METHOD This review synthesizes evidence from clinical trials and preclinical studies published in five years, identified through PubMed searches using keywords ("Deep Brain Stimulation" OR DBS) AND ("Treatment-Resistant Depression" OR TRD). Included studies encompassed clinical research (randomized/non-randomized trials, cohort studies) and mechanistic preclinical studies, excluding non-English publications and nonhuman experiments. Screening prioritized neuroanatomical targets (e.g., SCG, NAcc) and stimulation parameter optimization data. Examining the therapeutic mechanisms of DBS, the neuroanatomical targets utilized, and the clinical outcomes observed. It also discusses the challenges faced in DBS application and proposes potential technological advancements, such as closed-loop therapy and fiber tracking technology. FINDING Preliminary evidence exists regarding the efficacy and safety of DBS in the treatment of TRD in the subcortical cingulate gyrus (SCG), nucleus accumbens (NAcc), ventral capsule/ventral striatum (VC/VS), anterior limb of the internal capsule (ALIC), and so forth. Nevertheless, the optimal stimulation target remains undetermined. The review highlights the complexity of TRD and the need for personalized treatment strategies, noting that genetic, epigenetic, and neurophysiological changes are implicated in DBS's therapeutic effects. CONCLUSION In conclusion, while DBS for TRD remains an experimental therapy, it offers a unique and potentially effective treatment option for patients unresponsive to traditional treatments. The review emphasizes the need for further research to refine DBS targets and parameters, improve patient selection, and develop personalized treatment plans to enhance efficacy and safety in TRD management.
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Affiliation(s)
- Jianyang Dong
- Department of RehabilitationShenzhen University, Shenzhen University General HospitalShenzhenChina
| | - Mengying Dai
- Department of RehabilitationShenzhen Children's HospitalShenzhenChina
| | - Zinan Guo
- Department of RehabilitationShenzhen University, Shenzhen University General HospitalShenzhenChina
| | - Ting Xu
- Department of Neurology, Guangzhou First People's HospitalSouth China University of TechnologyGuangzhouChina
| | - Fangming Li
- Department of NeurologyShenzhen University, Shenzhen University General HospitalShenzhenChina
| | - Jianjun Li
- Department of RehabilitationShenzhen University, Shenzhen University General HospitalShenzhenChina
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Zhang B, Wu B, Zhang X, Xie H, Ling Y, Zhao Z, Gan R, Qiu L, Mechelli A, Jia Z, Gong Q. Gray matter structural alterations in first-episode drug-naïve adolescents with major depressive disorder: a comprehensive morphological analysis study. Psychol Med 2025; 55:e113. [PMID: 40211094 DOI: 10.1017/s0033291725000790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/12/2025]
Abstract
BACKGROUND Major depressive disorder (MDD) tends to emerge during adolescence; however, neurobiological research in adolescents has lagged behind that in adults. This study aimed to characterize gray matter (GM) structural alterations in adolescents with MDD using comprehensive morphological analyses. METHODS This study included 93 adolescent MDD patients and 77 healthy controls. Voxel-based morphometry (VBM), deformation-based morphometry (DBM), and surface-based morphometry (SBM) methods were used to analyze GM morphological alterations in adolescent MDD patients. Sex-by-group and age-by-group interactions, as well as the relationships between altered GM structure and clinical characteristics were also analyzed. RESULTS Whole-brain VBM and DBM analyses revealed GM atrophy in the left thalamus and bilateral midbrain in adolescent MDD patients. Whole-brain SBM analysis revealed that adolescent MDD patients, relative to controls, showed decreased thickness in the left postcentral gyrus and left precentral gyrus; increased thickness in the bilateral superior temporal gyrus, left parahippocampal gyrus and right lateral orbitofrontal gyrus; and decreased fractal dimension in the right lateral occipital gyrus. A significant sex-by-group interaction effect was found in the fractal dimension of the left lateral occipital gyrus. The volume of the left thalamus and the thickness of the left superior temporal gyrus were correlated with the duration of disease in adolescent MDD patients. CONCLUSIONS This study suggested that adolescent MDD had GM morphological abnormalities in the frontal-limbic, subcortical, perceptual network and midbrain regions, with some morphological abnormalities associated with disease duration and sex differences. These findings provide new insight into the neuroanatomical substrates underlying adolescent MDD.
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Affiliation(s)
- Baoshuai Zhang
- Department of Radiology, Huaxi MR Research Center (HMRRC), Institute of Radiology and Medical Imaging, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, China
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, China
| | - Baolin Wu
- Department of Radiology, Huaxi MR Research Center (HMRRC), Institute of Radiology and Medical Imaging, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, China
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, China
| | - Xun Zhang
- Department of Radiology, Huaxi MR Research Center (HMRRC), Institute of Radiology and Medical Imaging, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, China
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, China
| | - Hongsheng Xie
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, China
- Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Yanxin Ling
- Medical Imaging Center, The Second People's Hospital of Yibin, Yibin, China
| | - Ziru Zhao
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, China
- Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Ruoqiu Gan
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, China
- Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Lihua Qiu
- Medical Imaging Center, The Second People's Hospital of Yibin, Yibin, China
| | - Andrea Mechelli
- Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Zhiyun Jia
- Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Qiyong Gong
- Department of Radiology, Huaxi MR Research Center (HMRRC), Institute of Radiology and Medical Imaging, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, China
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, China
- Xiamen Key Laboratory of Psychoradiology and Neuromodulation, Department of Radiology, West China Xiamen Hospital of Sichuan University, Xiamen, China
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Cui B, Mocchi MM, Metzger BA, Kalva P, Magnotti JF, Fiedorowicz JG, Waters A, Kovach CK, Reed YY, Mathura RK, Steger C, Pascuzzi B, Kanja K, Veerakumar A, Tiruvadi V, Crowell A, Denison L, Rozell CJ, Pouratian N, Goodman W, Riva Posse P, Mayberg HS, Bijanki KR. Affective bias predicts changes in depression during deep brain stimulation therapy. Front Hum Neurosci 2025; 19:1539857. [PMID: 40201337 PMCID: PMC11977254 DOI: 10.3389/fnhum.2025.1539857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Accepted: 03/05/2025] [Indexed: 04/10/2025] Open
Abstract
Introduction Deep brain stimulation (DBS) is a promising treatment for refractory depression, utilizing surgically implanted electrodes to stimulate specific anatomical targets within the brain. However, limitations of patient-reported and clinician-administered mood assessments pose obstacles in evaluating DBS treatment efficacy. In this study, we investigated whether an affective bias task, which leverages the inherent negative interpretation bias seen in individuals with depression, could serve as a reliable measure of mood changes during DBS therapy in patients with treatment-resistant depression. Methods Two cohorts of patients (n = 8, n = 2) undergoing DBS for treatment-resistant depression at different academic medical centers completed an affective bias task at multiple time points before and after DBS implantation. The affective bias task involved rating the emotional content of a series of static photographic stimuli of facial expressions throughout their DBS treatment. Patients' ratings were compared with those of non-depressed controls to calculate affective bias scores. Linear mixed-effects modeling was used to assess changes in bias scores over time and their relationship with depression severity measured by the Hamilton Depression Rating Scale (HDRS-17). Results We observed significant improvements in total affective bias scores over the course of DBS treatment in both cohorts. Pre-DBS, patients exhibited a negative affective bias, which was nearly eliminated post-DBS, with total bias scores approaching those of non-depressed controls. Positive valence trials showed significant improvement post-DBS, while negative valence trials showed no notable change. A control analysis indicated that stimulation status did not significantly affect bias scores, and thus stimulation status was excluded from further modeling. Linear mixed-effects modeling revealed that more negative bias scores were associated with higher HDRS-17 scores, particularly for positive valence stimuli. Additionally, greater time elapsed since DBS implantation was associated with a decrease in HDRS-17 scores, indicating clinical improvement over time. Discussion Our findings demonstrate that the affective bias task leverages the inherent negative interpretation bias seen in individuals with depression, providing a standardized measure of how these biases change over time. Unlike traditional mood assessments, which rely on subjective introspection, the affective bias task consistently measures changes in mood, offering potential as a tool to monitor mood changes and evaluate the candidacy of DBS treatment in refractory depression.
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Affiliation(s)
- Brian Cui
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
| | - Madaline M. Mocchi
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
| | - Brian A. Metzger
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
| | - Prathik Kalva
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
| | - John F. Magnotti
- Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, United States
| | - Jess G. Fiedorowicz
- Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada
| | - Allison Waters
- Nash Family Center for Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Christopher K. Kovach
- Department of Neurosurgery, Carver College of Medicine, University of Iowa, Iowa City, IA, United States
| | - Yvonne Y. Reed
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
| | - Raissa K. Mathura
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
| | - Camille Steger
- Nash Family Center for Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Bailey Pascuzzi
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
| | - Kourtney Kanja
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
| | - Ashan Veerakumar
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States
| | - Vineet Tiruvadi
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States
- School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, United States
| | - Andrea Crowell
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States
| | - Lydia Denison
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States
| | - Christopher J. Rozell
- School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, United States
| | - Nader Pouratian
- Department of Neurosurgery, University of Texas Southwestern, Dallas, TX, United States
| | - Wayne Goodman
- Department of Psychiatry, Baylor College of Medicine, Houston, TX, United States
| | - Patricio Riva Posse
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States
| | - Helen S. Mayberg
- Department of Neurosurgery, Carver College of Medicine, University of Iowa, Iowa City, IA, United States
| | - Kelly Rowe Bijanki
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
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Dalrymple AN, Jones ST, Fallon JB, Shepherd RK, Weber DJ. Overcoming failure: improving acceptance and success of implanted neural interfaces. Bioelectron Med 2025; 11:6. [PMID: 40083033 PMCID: PMC11907899 DOI: 10.1186/s42234-025-00168-7] [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: 12/18/2024] [Accepted: 02/06/2025] [Indexed: 03/16/2025] Open
Abstract
Implanted neural interfaces are electronic devices that stimulate or record from neurons with the purpose of improving the quality of life of people who suffer from neural injury or disease. Devices have been designed to interact with neurons throughout the body to treat a growing variety of conditions. The development and use of implanted neural interfaces is increasing steadily and has shown great success, with implants lasting for years to decades and improving the health and quality of life of many patient populations. Despite these successes, implanted neural interfaces face a multitude of challenges to remain effective for the lifetime of their users. The devices are comprised of several electronic and mechanical components that each may be susceptible to failure. Furthermore, implanted neural interfaces, like any foreign body, will evoke an immune response. The immune response will differ for implants in the central nervous system and peripheral nervous system, as well as over time, ultimately resulting in encapsulation of the device. This review describes the challenges faced by developers of neural interface systems, particularly devices already in use in humans. The mechanical and technological failure modes of each component of an implant system is described. The acute and chronic reactions to devices in the peripheral and central nervous system and how they affect system performance are depicted. Further, physical challenges such as micro and macro movements are reviewed. The clinical implications of device failures are summarized and a guide for determining the severity of complication was developed and provided. Common methods to diagnose and examine mechanical, technological, and biological failure modes at various stages of development and testing are outlined, with an emphasis on chronic in vivo characterization of implant systems. Finally, this review concludes with an overview of some of the innovative solutions developed to reduce or resolve the challenges faced by implanted neural interface systems.
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Affiliation(s)
- Ashley N Dalrymple
- Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, USA.
- Department of Physical Medicine and Rehabilitation, University of Utah, Salt Lake City, UT, USA.
- NERVES Lab, University of Utah, Salt Lake City, UT, USA.
- Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
- NeuroMechatronics Lab, Carnegie Mellon University, Pittsburgh, PA, USA.
| | - Sonny T Jones
- Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, USA
- NERVES Lab, University of Utah, Salt Lake City, UT, USA
| | - James B Fallon
- Bionics Institute, St. Vincent's Hospital, Melbourne, VIC, Australia
- Medical Bionics Department, University of Melbourne, Melbourne, VIC, Australia
| | - Robert K Shepherd
- Bionics Institute, St. Vincent's Hospital, Melbourne, VIC, Australia
| | - Douglas J Weber
- Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA
- NeuroMechatronics Lab, Carnegie Mellon University, Pittsburgh, PA, USA
- Neuroscience Institute, Carnegie Mellon University, Pittsburgh, PA, USA
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5
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Mirkhani N, McNamara CG, Oliviers G, Sharott A, Duchet B, Bogacz R. Response of neuronal populations to phase-locked stimulation: model-based predictions and validation. J Neurosci 2025; 45:e2269242025. [PMID: 40068871 PMCID: PMC11984083 DOI: 10.1523/jneurosci.2269-24.2025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 02/06/2025] [Accepted: 03/01/2025] [Indexed: 04/12/2025] Open
Abstract
Modulation of neuronal oscillations holds promise for the treatment of neurological disorders. Nonetheless, conventional stimulation in a continuous open-loop manner can lead to side effects and suboptimal efficiency. Closed-loop strategies such as phase-locked stimulation aim to address these shortcomings by offering a more targeted modulation. While theories have been developed to understand the neural response to stimulation, their predictions have not been thoroughly tested using experimental data. Using a mechanistic coupled oscillator model, we elaborate on two key predictions describing the response to stimulation as a function of the phase and amplitude of ongoing neural activity. To investigate these predictions, we analyze electrocorticogram recordings from a previously conducted study in Parkinsonian rats, and extract the corresponding phase and response curves. We demonstrate that the amplitude response to stimulation is strongly correlated to the derivative of the phase response ([Formula: see text] > 0.8) in all animals except one, thereby validating a key model prediction. The second prediction postulates that the stimulation becomes ineffective when the network synchrony is high, a trend that appeared missing in the data. Our analysis explains this discrepancy by showing that the neural populations in Parkinsonian rats did not reach the level of synchrony for which the theory would predict ineffective stimulation. Our results highlight the potential of fine-tuning stimulation paradigms informed by mathematical models that consider both the ongoing phase and amplitude of the targeted neural oscillation.Significance Statement This study validates a mathematical model of coupled oscillators in predicting the response of neural activity to stimulation for the first time. Our findings also offer further insights beyond this validation. For instance, the demonstrated correlation between phase response and amplitude response is indeed a key theoretical concept within a subset of mathematical models. This prediction can bring about clinical implications in terms of predictive power for manipulation of neural activity. Additionally, while phase dependence in modulation has been previously studied, we propose a general framework for studying amplitude dependence as well. Lastly, our study reconciles the seemingly contradictory views of pathologic hypersynchrony and theoretical low synchrony in Parkinson's disease.
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Affiliation(s)
- Nima Mirkhani
- MRC Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX1 3TH, UK
| | - Colin G McNamara
- MRC Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX1 3TH, UK
- University College Cork, Cork T12 K8AF, Ireland
| | - Gaspard Oliviers
- MRC Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX1 3TH, UK
| | - Andrew Sharott
- MRC Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX1 3TH, UK
| | - Benoit Duchet
- MRC Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX1 3TH, UK
| | - Rafal Bogacz
- MRC Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX1 3TH, UK
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Wu B, Zhang X, Xie H, Zhang B, Ling Y, Gan R, Qiu L, Roberts N, Jia Z, Gong Q. Research Review: Shared and distinct structural and functional brain alterations in adolescents with major depressive disorder' - a multimodal meta-analysis. J Child Psychol Psychiatry 2024. [PMID: 39727198 DOI: 10.1111/jcpp.14104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/02/2024] [Indexed: 12/28/2024]
Abstract
BACKGROUND Neuroimaging studies have identified brain structural and functional alterations in adolescents with major depressive disorder (MDD); however, the results are inconsistent, and whether patients exhibit spatially convergent structural and functional brain abnormalities remains unclear. METHODS We conducted voxel-wise meta-analysis of voxel-based morphometry (VBM) and resting-state functional studies, respectively, to identify regional gray matter volume (GMV) and brain activity alterations in adolescent MDD patients. Multimodal analysis was performed to examine the overlap of regional GMV and brain activity alterations. Meta-regression analysis was conducted to evaluate the potential effects of clinical variables. RESULTS Ten whole-brain VBM studies (403 patients and 319 controls) and 14 resting-state functional studies (510 patients and 474 controls) were included. Adolescent MDD patients showed conjoint structural and functional alterations in the left medial/dorsolateral prefrontal cortex, lateral temporal cortex and sensorimotor regions, and left insula. Adolescent MDD patients showed structural-specific abnormalities in the subcortical and prefrontal-limbic regions and functional-specific abnormalities in the right insula, right superior occipital gyrus, left inferior frontal gyrus and left precuneus. Meta-regression analyses revealed that the mean age of adolescents with MDD was positively associated with GMV in the right superior temporal gyrus and negatively associated with brain activity in the right insula, and the symptom severity of adolescents with MDD was positively associated with brain activity in the right superior occipital gyrus. CONCLUSIONS This meta-analysis identified complicated patterns of conjoint and dissociated brain alterations in adolescent MDD patients, which may advance our understanding of the neurobiology of adolescent MDD.
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Affiliation(s)
- Baolin Wu
- Department of Radiology and Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, China
| | - Xun Zhang
- Department of Radiology and Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, China
| | - Hongsheng Xie
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, China
- Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Baoshuai Zhang
- Department of Radiology and Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, China
| | - Yanxin Ling
- Medical Imaging Center, The Second People's Hospital of Yibin, Yibin, China
| | - Ruoqiu Gan
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, China
- Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Lihua Qiu
- Medical Imaging Center, The Second People's Hospital of Yibin, Yibin, China
| | - Neil Roberts
- The Queens Medical Research Institute (QMRI), School of Clinical Sciences, University of Edinburgh, Edinburgh, UK
| | - Zhiyun Jia
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, China
- Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Qiyong Gong
- Department of Radiology and Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, China
- Department of Radiology, West China Xiamen Hospital of Sichuan University, Xiamen, China
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Tamura Y, Maeda S, Takahashi H, Aoto Y, Matsuki T, Seki K. GABAergic circuit interaction between central amygdala and bed nucleus of the stria terminalis in lipopolysaccharide-induced despair-like behavior. Physiol Behav 2024; 288:114753. [PMID: 39551417 DOI: 10.1016/j.physbeh.2024.114753] [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: 10/05/2024] [Revised: 11/12/2024] [Accepted: 11/14/2024] [Indexed: 11/19/2024]
Abstract
Hyperexcitability of central amygdala (CeA) induces depressive symptoms. The bed nucleus of the stria terminalis (BNST) receives GABAergic input from the CeA. However, it remains unclear whether the GABAergic neurons in the CeA projecting to BNST contribute to major depression. Here, we investigated the roles of GABAergic neurons in CeA and BNST in lipopolysaccharide (LPS)-induced despair-like behavior. We generated adeno-associated virus vectors (AAV) carrying shRNA against Gad67 to knock down GAD67 expression in CeA (Gad67-KD-CeA) or BNST (Gad67-KD-BNST) in C57BL/6J male mice. Despair-like behavior was assessed by tail suspension test (TST) 24 h after LPS administration. Saline-treated Gad67-KD-CeA mice exhibited longer immobility during TST than saline-treated AAV-injected control (AAV-Cont) mice. Although LPS increased immobility time in AAV-Cont mice, it did not affect immobility time in Gad67-KD-CeA mice. While LPS did not affect the immobility time in Gad67-KD-BNST mice, it increased immobility time in AAV-Cont mice. We injected GFP-expressing AAV with a Dlx promoter, specifically expressed in GABAergic neurons, into CeA, and FluoroGold, a retrograde neuronal tracer, into the BNST. GFP signals associated with CeA GABAergic neurons were detected in the BNST, contacting c-fos and GAD67-expressed cells following LPS. We detected the FluoroGold signals in GAD67- and c-fos-expressed neurons in the CeA after LPS administration. Bilateral intra-BNST injection of muscimol (2 pmol), a GABAA receptor agonist, increased immobility time during TST. These findings suggest that LPS-decreased GABAergic activity in the CeA may lead to disinhibition of GABAergic interneurons in the BNST, resulting in GABAA receptor activation and subsequently induces despair-like behavior.
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Affiliation(s)
- Yuka Tamura
- Department of Pharmacology, School of Pharmaceutical Science, Ohu University, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611, Japan
| | - Sakura Maeda
- Department of Pharmacology, School of Pharmaceutical Science, Ohu University, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611, Japan
| | - Haruna Takahashi
- Department of Pharmacology, School of Pharmaceutical Science, Ohu University, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611, Japan
| | - Yuta Aoto
- Department of Pharmacology, School of Pharmaceutical Science, Ohu University, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611, Japan
| | - Tohru Matsuki
- Department of Cellular Pathology, Institute for Developmental Research, Aichi Developmental Disability Center, Kasugai, Aichi 480-0392, Japan.
| | - Kenjiro Seki
- Department of Pharmacology, School of Pharmaceutical Science, Ohu University, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611, Japan.
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Fujimoto S, Fujimoto A, Elorette C, Choi KS, Mayberg H, Russ B, Rudebeck P. What can neuroimaging of neuromodulation reveal about the basis of circuit therapies for psychiatry? Neuropsychopharmacology 2024; 50:184-195. [PMID: 39198580 PMCID: PMC11526173 DOI: 10.1038/s41386-024-01976-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 07/23/2024] [Accepted: 07/29/2024] [Indexed: 09/01/2024]
Abstract
Neuromodulation is increasingly becoming a therapeutic option for treatment resistant psychiatric disorders. These non-invasive and invasive therapies are still being refined but are clinically effective and, in some cases, provide sustained symptom reduction. Neuromodulation relies on changing activity within a specific brain region or circuit, but the precise mechanisms of action of these therapies, is unclear. Here we review work in both humans and animals that has provided insight into how therapies such as deep brain and transcranial magnetic stimulation alter neural activity across the brain. We focus on studies that have combined neuromodulation with neuroimaging such as PET and MRI as these measures provide detailed information about the distributed networks that are modulated and thus insight into both the mechanisms of action of neuromodulation but also potentially the basis of psychiatric disorders. Further we highlight work in nonhuman primates that has revealed how neuromodulation changes neural activity at different scales from single neuron activity to functional connectivity, providing key insight into how neuromodulation influences the brain. Ultimately, these studies highlight the value of combining neuromodulation with neuroimaging to reveal the mechanisms through which these treatments influence the brain, knowledge vital for refining targeted neuromodulation therapies for psychiatric disorders.
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Affiliation(s)
- Satoka Fujimoto
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Lipschultz Center for Cognitive Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Atsushi Fujimoto
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Lipschultz Center for Cognitive Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Catherine Elorette
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Lipschultz Center for Cognitive Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ki Sueng Choi
- Nash Family Center for Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Departments of Radiology and Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Helen Mayberg
- Nash Family Center for Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Departments of Radiology and Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Neurology and Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Brian Russ
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Lipschultz Center for Cognitive Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute, Orangeburg, NY, USA.
- Department of Psychiatry, New York University at Langone, New York, NY, USA.
| | - Peter Rudebeck
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Lipschultz Center for Cognitive Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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9
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Wischnewski M, Shirinpour S, Alekseichuk I, Lapid MI, Nahas Z, Lim KO, Croarkin PE, Opitz A. Real-time TMS-EEG for brain state-controlled research and precision treatment: a narrative review and guide. J Neural Eng 2024; 21:061001. [PMID: 39442548 PMCID: PMC11528152 DOI: 10.1088/1741-2552/ad8a8e] [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: 02/01/2024] [Revised: 10/13/2024] [Accepted: 10/23/2024] [Indexed: 10/25/2024]
Abstract
Transcranial magnetic stimulation (TMS) modulates neuronal activity, but the efficacy of an open-loop approach is limited due to the brain state's dynamic nature. Real-time integration with electroencephalography (EEG) increases experimental reliability and offers personalized neuromodulation therapy by using immediate brain states as biomarkers. Here, we review brain state-controlled TMS-EEG studies since the first publication several years ago. A summary of experiments on the sensorimotor mu rhythm (8-13 Hz) shows increased cortical excitability due to TMS pulse at the trough and decreased excitability at the peak of the oscillation. Pre-TMS pulse mu power also affects excitability. Further, there is emerging evidence that the oscillation phase in theta and beta frequency bands modulates neural excitability. Here, we provide a guide for real-time TMS-EEG application and discuss experimental and technical considerations. We consider the effects of hardware choice, signal quality, spatial and temporal filtering, and neural characteristics of the targeted brain oscillation. Finally, we speculate on how closed-loop TMS-EEG potentially could improve the treatment of neurological and mental disorders such as depression, Alzheimer's, Parkinson's, schizophrenia, and stroke.
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Affiliation(s)
- Miles Wischnewski
- Department of Psychology, Experimental Psychology, University of Groningen, Groningen, The Netherlands
- Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, United States of America
| | - Sina Shirinpour
- Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, United States of America
| | - Ivan Alekseichuk
- Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, United States of America
- Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, IL, United States of America
| | - Maria I Lapid
- Department of Psychiatry & Psychology, Mayo Clinic, Rochester, MN, United States of America
| | - Ziad Nahas
- Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, United States of America
| | - Kelvin O Lim
- Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, United States of America
| | - Paul E Croarkin
- Department of Psychiatry & Psychology, Mayo Clinic, Rochester, MN, United States of America
| | - Alexander Opitz
- Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, United States of America
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10
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Wei C, Yang Q, Chen J, Rao X, Li Q, Luo J. EEG microstate as a biomarker of post-stroke depression with acupuncture treatment. Front Neurol 2024; 15:1452243. [PMID: 39534268 PMCID: PMC11554454 DOI: 10.3389/fneur.2024.1452243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 10/14/2024] [Indexed: 11/16/2024] Open
Abstract
Background Post-stroke depression (PSD) is a prevalent psychiatric complication among stroke survivors. The PSD researches focus on pathogenesis, new treatment methods and efficacy prediction. This study explored the electroencephalography (EEG) microstates in PSD and assessed their changes after acupuncture treatment, aiming to find the biological characteristics and the predictors of treatment efficacy of PSD. Methods A 64-channel resting EEG data was collected from 70 PSD patients (PSD group) and 40 healthy controls (HC group) to explore the neuro-electrophysiological mechanism of PSD. The PSD patients received 6 weeks of acupuncture treatment. EEG data was collected from 60 PSD patients after acupuncture treatment (MA group) to verify whether acupuncture had a modulating effect on abnormal EEG microstates. Finally, the MA group was divided into two groups: the remission prediction group (RP group) and the non-remission prediction group (NRP group) according to the 24-Item Hamilton Depression Scale (HAMD-24) reduction rate. A prediction model for acupuncture treatment was established by baseline EEG microstates. Results The duration of microstate D along with the occurrence and contribution of microstate C were reduced in PSD patients. Acupuncture treatment partially normalized abnormal EEG microstates in PSD patients. Baseline EEG microstates predicted the efficacy of acupuncture treatment with an area under the curve (AUC) of 0.964. Conclusion This study provides a novel viewpoint on the neurophysiological mechanisms of PSD and emphasizes the potential of EEG microstates as a functional biomarker. Additionally, we anticipated the therapeutic outcomes of acupuncture by analyzing the baseline microstates, which holds significant practical implication for the PSD treatment.
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Affiliation(s)
| | | | | | | | | | - Jun Luo
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China
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11
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Xu Q, Chen Y, Miller S, Bajaj K, Santana J, Badawy M, Lyu H, Liu Y, He N, Yan F, Haacke EM. In Vivo visualization of white matter fiber tracts in the brainstem using low flip angle double echo 3D gradient echo imaging at 3T. Neuroimage 2024; 300:120857. [PMID: 39299660 DOI: 10.1016/j.neuroimage.2024.120857] [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: 07/15/2024] [Revised: 09/11/2024] [Accepted: 09/17/2024] [Indexed: 09/22/2024] Open
Abstract
BACKGROUND White matter (WM) fiber tracts in the brainstem communicate with various regions in the cerebrum, cerebellum, and spinal cord. Clinically, small lesions, malformations, or histopathological changes in the brainstem can cause severe neurological disorders. A direct and non-invasive assessment approach could bring valuable information about the intricate anatomical variations of the white matter fiber tracts and nuclei. Although tractography from diffusion tensor imaging has been commonly used to map the WM fiber tracts connectivity, it is difficult to differentiate the complex WM tracts anatomically. Both high field MRI methods and ultrahigh-field MRI methods at 7T and 11.7 T have been used to enhance the contrast of WM fiber tracts. Despite their promising results, it is still challenging to achieve wide clinical adoption at 3T. In this study, we explored a clinically feasible method using a proton density weighted (PDW) 3D gradient echo (GRE) sequence to directly image the WM fiber tracts in the brainstem at 3T in vivo. METHODS We optimized a 3D high resolution, double echo, short TR, PDW GRE sequence on 5 healthy volunteers using a clinical 3T scanner to visualize the complicated anatomy of WM fiber tracts in the brain stem. Tissue properties including T1, proton density and T2* from in vivo quantitative MRI data were used for simulations to determine the optimal flip angle for the sequence. The visualization of multiple WM fiber tracts in the brainstem was assessed qualitatively and quantitatively using relative contrast and contrast-to-noise ratio (CNR). To improve the CNR, the final images were created by averaging over all echoes from two consecutive scans at the optimal flip angle. The results were compared to anatomical atlases and histology sections to identify the major fiber tracts. All the identified major fiber tracts were labeled on axial, sagittal and coronal slices. RESULTS The WM fiber tracts were found to have distinct hypointense signal throughout the brainstem and most of the major WM fiber tracts, such as the corticospinal tract, medial lemniscus, medial longitudinal fasciculus, and central tegmental tract, in the brainstem up to and including the thalamus were identified in all subjects. Both qualitative and quantitative evaluations showed that the 3° scan offered the best contrast for WM fiber tracts for a TR of 20 ms. The average over the first two echo times and two consecutive 3° scans gave a CNR of 47.8 ± 6.2 for the pyramidal tracts in particular and CNRs values greater than 6.5 ± 2.4 for the rest of the fiber tracts. CONCLUSIONS All the major fiber tracts in the brainstem could be visualized. Given the reasonably short scan time of 10 min at 3T, double echo PDW GRE sequence is a very practical approach for clinical adoption.
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Affiliation(s)
- Qiuyun Xu
- Department of Radiology, Wayne State University, 3990 John R, 4201 St Antoine, Detroit Receiving Hospital 3L-8, Detroit, MI, 48201, USA
| | - Yongsheng Chen
- Department of Neurology, Detroit Medical Center, Wayne State University, University Health Center-8th floor, 4201 St Antoine, Detroit, MI, 48201, USA
| | - Stephan Miller
- Department of Radiology, Detroit Medical Center, Wayne State University School of Medicine, 3901 Beaubien Boulevard, Detroit, MI, 48201, USA
| | - Kunal Bajaj
- Department of Radiology, Detroit Medical Center, Wayne State University School of Medicine, 3901 Beaubien Boulevard, Detroit, MI, 48201, USA
| | - Jairo Santana
- Department of Radiology, Detroit Medical Center, Wayne State University School of Medicine, 3901 Beaubien Boulevard, Detroit, MI, 48201, USA
| | - Mohamed Badawy
- Department of Radiology, Detroit Medical Center, Wayne State University School of Medicine, 3901 Beaubien Boulevard, Detroit, MI, 48201, USA
| | - Haiying Lyu
- Department of Radiology, Ruijin Hospital, No. 197 Ruijin Er Road, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Yu Liu
- Department of Radiology, Ruijin Hospital, No. 197 Ruijin Er Road, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Naying He
- Department of Radiology, Ruijin Hospital, No. 197 Ruijin Er Road, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Fuhua Yan
- Department of Radiology, Ruijin Hospital, No. 197 Ruijin Er Road, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
| | - E Mark Haacke
- Department of Radiology, Wayne State University, 3990 John R, 4201 St Antoine, Detroit Receiving Hospital 3L-8, Detroit, MI, 48201, USA; Department of Neurology, Detroit Medical Center, Wayne State University, University Health Center-8th floor, 4201 St Antoine, Detroit, MI, 48201, USA; Department of Radiology, Ruijin Hospital, No. 197 Ruijin Er Road, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Department of Biomedical Engineering, Wayne State University, 3990 John R, 4201 St Antoine, Detroit Receiving Hospital 3L-8, Detroit, MI, 48201, USA.
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12
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Yamashiro K, Matsumoto N, Ikegaya Y. Diffusion model-based image generation from rat brain activity. PLoS One 2024; 19:e0309709. [PMID: 39240852 PMCID: PMC11379174 DOI: 10.1371/journal.pone.0309709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 08/16/2024] [Indexed: 09/08/2024] Open
Abstract
Brain-computer interface (BCI) technology has gained recognition in various fields, including clinical applications, assistive technology, and human-computer interaction research. BCI enables communication, control, and monitoring of the affective/cognitive states of users. Recently, BCI has also found applications in the artistic field, enabling real-time art composition using brain activity signals, and engaging performers, spectators, or an entire audience with brain activity-based artistic environments. Existing techniques use specific features of brain activity, such as the P300 wave and SSVEPs, to control drawing tools, rather than directly reflecting brain activity in the output image. In this study, we present a novel approach that uses a latent diffusion model, a type of deep neural network, to generate images directly from continuous brain activity. We demonstrate this technology using local field potentials from the neocortex of freely moving rats. This system continuously converted the recorded brain activity into images. Our end-to-end method for generating images from brain activity opens new possibilities for creative expression and experimentation. Notably, our results show that the generated images successfully reflect the dynamic and stochastic nature of the underlying neural activity, providing a unique procedure for visualization of brain function.
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Affiliation(s)
- Kotaro Yamashiro
- Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
| | - Nobuyoshi Matsumoto
- Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
- Institute for AI and Beyond, The University of Tokyo, Tokyo, Japan
| | - Yuji Ikegaya
- Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
- Institute for AI and Beyond, The University of Tokyo, Tokyo, Japan
- Center for Information and Neural Networks, National Institute of Information and Communications Technology, Suita City, Osaka, Japan
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13
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Haidary M, Arif S, Hossaini D, Madadi S, Akbari E, Rezayee H. Pain-Insomnia-Depression Syndrome: Triangular Relationships, Pathobiological Correlations, Current Treatment Modalities, and Future Direction. Pain Ther 2024; 13:733-744. [PMID: 38814408 PMCID: PMC11255165 DOI: 10.1007/s40122-024-00614-5] [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: 03/06/2024] [Accepted: 05/10/2024] [Indexed: 05/31/2024] Open
Abstract
Pain-insomnia-depression syndrome (PIDS) is a complex triad of chronic pain, insomnia, and depression that has profound effects on an individual's quality of life and mental health. The pathobiological context of PIDS involves complex neurobiological and physiological mechanisms, including alterations in neurotransmitter systems and impaired pain processing pathways. The first-line therapeutic approaches for the treatment of chronic pain, depression, and insomnia are a combination of pharmacological and non-pharmacological therapies. In cases where patients do not respond adequately to these treatments, additional interventions such as deep brain stimulation (DBS) may be required. Despite advances in understanding and treatment, there are still gaps in knowledge that need to be addressed. To improve our understanding, future research should focus on conducting longitudinal studies to uncover temporal associations, identify biomarkers and genetic markers associated with PIDS, examine the influence of psychosocial factors on treatment responses, and develop innovative interventions that address the complex nature of PIDS. The aim of this study is to provide a comprehensive overview of these components and to discuss their underlying pathobiological relationships.
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Affiliation(s)
- Murtaza Haidary
- Medical Research and Technology Center, Khatam Al-Nabieen University, Kabul, Afghanistan.
| | - Shamim Arif
- Medical Research Center, Kateb University, Kabul, Afghanistan
| | - Dawood Hossaini
- Department of Biology and Microbiology, Faculty of Medical Laboratory Technology, Khatam Al-Nabieen University, Kabul, Afghanistan
| | - Shekiba Madadi
- Medical Research Center, Kateb University, Kabul, Afghanistan
| | - Elham Akbari
- Department of Biology and Microbiology, Faculty of Medical Laboratory Technology, Khatam Al-Nabieen University, Kabul, Afghanistan
| | - Hossain Rezayee
- Department of Chemistry and Biochemistry, Faculty of Medical Laboratory Technology, Khatam Al-Nabieen University, Kabul, Afghanistan
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14
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Sadeghzadeh S, Swaminathan A, Bhanot P, Steeman S, Xu A, Shah V, Purger DA, Buch VP. Emerging Outlook on Personalized Neuromodulation for Depression: Insights From Tractography-Based Targeting. BIOLOGICAL PSYCHIATRY. COGNITIVE NEUROSCIENCE AND NEUROIMAGING 2024; 9:754-764. [PMID: 38679323 DOI: 10.1016/j.bpsc.2024.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 03/07/2024] [Accepted: 04/11/2024] [Indexed: 05/01/2024]
Abstract
BACKGROUND Deep brain stimulation has shown promise in treating individual patients with treatment-resistant depression, but larger-scale trials have been less successful. Here, we created what is, to our knowledge, the largest meta-analysis with individual patient data to date to explore whether the use of tractography enhances the efficacy of deep brain stimulation for treatment-resistant depression. METHODS We systematically reviewed 1823 articles, selecting 32 that contributed data from 366 patients. We stratified the individual patient data based on stimulation target and use of tractography. Using 2-way type III analysis of variance, Welch's 2-sample t tests, and mixed-effects linear regression models, we evaluated changes in depression severity 1 year (9-15 months) postoperatively and at last follow-up (4 weeks to 8 years) as assessed by depression scales. RESULTS Tractography was used for medial forebrain bundle (MFB) (n = 17 tractography/32 total), subcallosal cingulate (SCC) (n = 39 tractography/241 total), and ventral capsule/ventral striatum (n = 3 tractography/41 total) targets; it was not used for bed nucleus of stria terminalis (n = 11), lateral habenula (n = 10), and inferior thalamic peduncle (n = 1). Across all patients, tractography significantly improved mean depression scores at 1 year (p < .001) and last follow-up (p = .009). Within the target cohorts, tractography improved depression scores at 1 year for both MFB and SCC, though significance was met only at the α = 0.1 level (SCC: β = 15.8%, p = .09; MFB: β = 52.4%, p = .10). Within the tractography cohort, patients with MFB tractography showed greater improvement than patients with SCC tractography (72.42 ± 7.17% vs. 54.78 ± 4.08%) at 1 year (p = .044). CONCLUSIONS Our findings underscore the promise of tractography in deep brain stimulation for treatment-resistant depression as a method for personalization of therapy, supporting its inclusion in future trials.
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Affiliation(s)
- Sina Sadeghzadeh
- Department of Neurosurgery, Stanford University, Stanford, California.
| | | | - Priya Bhanot
- Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Samantha Steeman
- Department of Neurosurgery, Stanford University, Stanford, California
| | - Audrey Xu
- Department of Neurosurgery, Stanford University, Stanford, California
| | - Vaibhavi Shah
- Department of Neurosurgery, Stanford University, Stanford, California
| | - David A Purger
- Department of Neurosurgery, Stanford University, Stanford, California
| | - Vivek P Buch
- Department of Neurosurgery, Stanford University, Stanford, California.
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15
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Meyer GM, Hollunder B, Li N, Butenko K, Dembek TA, Hart L, Nombela C, Mosley P, Akram H, Acevedo N, Borron BM, Chou T, Castaño Montoya JP, Strange B, Barcia JA, Tyagi H, Castle DJ, Smith AH, Choi KS, Kopell BH, Mayberg HS, Sheth SA, Goodman WK, Leentjens AFG, Richardson RM, Rossell SL, Bosanac P, Cosgrove GR, Kuhn J, Visser-Vandewalle V, Figee M, Dougherty DD, Siddiqi SH, Zrinzo L, Joyce E, Baldermann JC, Fox MD, Neudorfer C, Horn A. Deep Brain Stimulation for Obsessive-Compulsive Disorder: Optimal Stimulation Sites. Biol Psychiatry 2024; 96:101-113. [PMID: 38141909 PMCID: PMC11190041 DOI: 10.1016/j.biopsych.2023.12.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 12/06/2023] [Accepted: 12/13/2023] [Indexed: 12/25/2023]
Abstract
BACKGROUND Deep brain stimulation (DBS) is a promising treatment option for treatment-refractory obsessive-compulsive disorder (OCD). Several stimulation targets have been used, mostly in and around the anterior limb of the internal capsule and ventral striatum. However, the precise target within this region remains a matter of debate. METHODS Here, we retrospectively studied a multicenter cohort of 82 patients with OCD who underwent DBS of the ventral capsule/ventral striatum and mapped optimal stimulation sites in this region. RESULTS DBS sweet-spot mapping performed on a discovery set of 58 patients revealed 2 optimal stimulation sites associated with improvements on the Yale-Brown Obsessive Compulsive Scale, one in the anterior limb of the internal capsule that overlapped with a previously identified OCD-DBS response tract and one in the region of the inferior thalamic peduncle and bed nucleus of the stria terminalis. Critically, the nucleus accumbens proper and anterior commissure were associated with beneficial but suboptimal clinical improvements. Moreover, overlap with the resulting sweet- and sour-spots significantly estimated variance in outcomes in an independent cohort of 22 patients from 2 additional DBS centers. Finally, beyond obsessive-compulsive symptoms, stimulation of the anterior site was associated with optimal outcomes for both depression and anxiety, while the posterior site was only associated with improvements in depression. CONCLUSIONS Our results suggest how to refine targeting of DBS in OCD and may be helpful in guiding DBS programming in existing patients.
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Affiliation(s)
- Garance M Meyer
- Center for Brain Circuit Therapeutics, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
| | - Barbara Hollunder
- Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany; Einstein Center for Neurosciences Berlin, Charité Universitätsmedizin Berlin, Berlin, Germany; Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Ningfei Li
- Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Konstantin Butenko
- Center for Brain Circuit Therapeutics, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Till A Dembek
- Department of Neurology, Faculty of Medicine, University of Cologne, Cologne, Germany
| | - Lauren Hart
- Center for Brain Circuit Therapeutics, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Cristina Nombela
- Biological and Health Psychology, School of Psychology, Universidad Autónoma de Madrid, Madrid, Spain
| | - Philip Mosley
- Clinical Brain Networks Group, QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland, Australia; Neurosciences Queensland, St. Andrew's War Memorial Hospital, Spring Hill, Queensland, Australia; Queensland Brain Institute, University of Queensland, St. Lucia, Brisbane, Queensland, Australia; Australian e-Health Research Centre, Commonwealth Scientific and Industrial Research Organisation Health and Biosecurity, Herston, Queensland, Australia
| | - Harith Akram
- Department of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, United Kingdom; National Hospital for Neurology and Neurosurgery, University College London Queen Square Institute of Neurology, London, United Kingdom
| | - Nicola Acevedo
- Centre for Mental Health, Swinburne University, Melbourne, Victoria, Australia; St. Vincent's Hospital, Melbourne, Victoria, Australia
| | - Benjamin M Borron
- Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Tina Chou
- Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Juan Pablo Castaño Montoya
- Department of Neurosurgery, Hospital Clínico San Carlos, Instituto de Investigacion Sanitaria San Carlos, Universidad Complutense de Madrid, Madrid, Spain
| | - Bryan Strange
- Laboratory for Clinical Neuroscience, Center for Biomedical Technology, Universidad Politécnica de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, Spain
| | - Juan A Barcia
- Department of Neurosurgery, Hospital Clínico San Carlos, Instituto de Investigacion Sanitaria San Carlos, Universidad Complutense de Madrid, Madrid, Spain
| | - Himanshu Tyagi
- Department of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, United Kingdom; National Hospital for Neurology and Neurosurgery, University College London Queen Square Institute of Neurology, London, United Kingdom
| | - David J Castle
- University of Tasmania and Centre for Mental Health Service Innovation, Tasmania, Australia; State-wide Mental Health Service, Tasmania, Australia
| | - Andrew H Smith
- Nash Family Center for Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Ki Sueng Choi
- Nash Family Center for Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Brian H Kopell
- Nash Family Center for Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Helen S Mayberg
- Nash Family Center for Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Sameer A Sheth
- Department of Electrical and Computer Engineering, Rice University, Houston, Texas; Department of Psychiatry and Behavioral Science, Baylor College of Medicine, Houston, Texas
| | - Wayne K Goodman
- Department of Electrical and Computer Engineering, Rice University, Houston, Texas; Department of Psychiatry and Behavioral Science, Baylor College of Medicine, Houston, Texas
| | - Albert F G Leentjens
- Department of Psychiatry, Maastricht University Medical Center, Maastricht, the Netherlands
| | - R Mark Richardson
- Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Susan L Rossell
- Centre for Mental Health, Swinburne University, Melbourne, Victoria, Australia; St. Vincent's Hospital, Melbourne, Victoria, Australia
| | - Peter Bosanac
- St. Vincent's Hospital, Melbourne, Victoria, Australia; Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia
| | - G Rees Cosgrove
- Center for Brain Circuit Therapeutics, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Jens Kuhn
- Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, Johanniter Hospital Oberhausen, EVKLN, Oberhausen, Germany
| | - Veerle Visser-Vandewalle
- Department of Stereotactic and Functional Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Martijn Figee
- Nash Family Center for Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Darin D Dougherty
- Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Shan H Siddiqi
- Center for Brain Circuit Therapeutics, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Ludvic Zrinzo
- Department of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, United Kingdom; National Hospital for Neurology and Neurosurgery, University College London Queen Square Institute of Neurology, London, United Kingdom
| | - Eileen Joyce
- Department of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, United Kingdom; National Hospital for Neurology and Neurosurgery, University College London Queen Square Institute of Neurology, London, United Kingdom
| | - Juan Carlos Baldermann
- Department of Neurology, Faculty of Medicine, University of Cologne, Cologne, Germany; Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Michael D Fox
- Center for Brain Circuit Therapeutics, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Clemens Neudorfer
- Center for Brain Circuit Therapeutics, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Andreas Horn
- Center for Brain Circuit Therapeutics, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany; Einstein Center for Neurosciences Berlin, Charité Universitätsmedizin Berlin, Berlin, Germany; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
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16
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Wilson MG, Riis TS, Kubanek J. Controlled ultrasonic interventions through the human skull. Front Hum Neurosci 2024; 18:1412921. [PMID: 38979100 PMCID: PMC11228146 DOI: 10.3389/fnhum.2024.1412921] [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: 04/08/2024] [Accepted: 06/03/2024] [Indexed: 07/10/2024] Open
Abstract
Transcranial focused ultrasound enables precise and non-invasive manipulations of deep brain circuits in humans, promising to provide safe and effective treatments of various neurological and mental health conditions. Ultrasound focused to deep brain targets can be used to modulate neural activity directly or localize the release of psychoactive drugs. However, these applications have been impeded by a key barrier-the human skull, which attenuates ultrasound strongly and unpredictably. To address this issue, we have developed an ultrasound-based approach that directly measures and compensates for the ultrasound attenuation by the skull. No additional skull imaging, simulations, assumptions, or free parameters are necessary; the method measures the attenuation directly by emitting a pulse of ultrasound from an array on one side of the head and measuring with an array on the opposite side. Here, we apply this emerging method to two primary future uses-neuromodulation and local drug release. Specifically, we show that the correction enables effective stimulation of peripheral nerves and effective release of propofol from nanoparticle carriers through an ex vivo human skull. Neither application was effective without the correction. Moreover, the effects show the expected dose-response relationship and targeting specificity. This article highlights the need for precise control of ultrasound intensity within the skull and provides a direct and practical approach for addressing this lingering barrier.
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Affiliation(s)
- Matthew G Wilson
- Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, United States
| | - Thomas S Riis
- Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, United States
| | - Jan Kubanek
- Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, United States
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17
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Nothdurfter D, Jawinski P, Markett S. White Matter Tract Integrity Is Reduced in Depression and in Individuals With Genetic Liability to Depression. Biol Psychiatry 2024; 95:1063-1071. [PMID: 38103877 DOI: 10.1016/j.biopsych.2023.11.028] [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: 02/20/2023] [Revised: 11/06/2023] [Accepted: 11/26/2023] [Indexed: 12/19/2023]
Abstract
BACKGROUND While major depression has been linked to changes in white matter architecture, it remains unclear whether risk factors for depression are directly associated with these alterations. We reexamined white matter fiber tracts in individuals with depressive symptoms and investigated the connection between genetic and environmental risk for depression and structural changes in the brain. METHODS We included 19,183 participants from the UK Biobank imaging cohort, with depression status and adverse life experience based on questionnaire data and genetic liability for depression quantified by polygenic scores. The integrity of 27 white matter tracts was assessed using mean fractional anisotropy derived from diffusion magnetic resonance imaging. RESULTS White matter integrity was reduced, particularly in thalamic and intracortical fiber tracts, in individuals with depressive symptoms, independent of current symptom status. In a group of healthy individuals without depression, increasing genetic risk and increasing environmental risk were associated with reduced integrity in relevant fiber tracts, particularly in thalamic radiations. This association was stronger than expected based on statistical dependencies between samples, as confirmed by subsequent in silico simulations and permutation tests. CONCLUSIONS White matter alterations in thalamic and association tracts are associated with depressive symptoms and genetic risk for depression in unaffected individuals, suggesting an intermediate phenotype at the brain level.
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Affiliation(s)
- David Nothdurfter
- Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Philippe Jawinski
- Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Sebastian Markett
- Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.
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18
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Varela RB, Boschen SL, Yates N, Houghton T, Blaha CD, Lee KH, Bennet KE, Kouzani AZ, Berk M, Quevedo J, Valvassori SS, Tye SJ. Anti-manic effect of deep brain stimulation of the ventral tegmental area in an animal model of mania induced by methamphetamine. Bipolar Disord 2024; 26:376-387. [PMID: 38558302 DOI: 10.1111/bdi.13423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/04/2024]
Abstract
BACKGROUND Treatment of refractory bipolar disorder (BD) is extremely challenging. Deep brain stimulation (DBS) holds promise as an effective treatment intervention. However, we still understand very little about the mechanisms of DBS and its application on BD. AIM The present study aimed to investigate the behavioural and neurochemical effects of ventral tegmental area (VTA) DBS in an animal model of mania induced by methamphetamine (m-amph). METHODS Wistar rats were given 14 days of m-amph injections, and on the last day, animals were submitted to 20 min of VTA DBS in two different patterns: intermittent low-frequency stimulation (LFS) or continuous high-frequency stimulation (HFS). Immediately after DBS, manic-like behaviour and nucleus accumbens (NAc) phasic dopamine (DA) release were evaluated in different groups of animals through open-field tests and fast-scan cyclic voltammetry. Levels of NAc dopaminergic markers were evaluated by immunohistochemistry. RESULTS M-amph induced hyperlocomotion in the animals and both DBS parameters reversed this alteration. M-amph increased DA reuptake time post-sham compared to baseline levels, and both LFS and HFS were able to block this alteration. LFS was also able to reduce phasic DA release when compared to baseline. LFS was able to increase dopamine transporter (DAT) expression in the NAc. CONCLUSION These results demonstrate that both VTA LFS and HFS DBS exert anti-manic effects and modulation of DA dynamics in the NAc. More specifically the increase in DA reuptake driven by increased DAT expression may serve as a potential mechanism by which VTA DBS exerts its anti-manic effects.
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Affiliation(s)
- Roger B Varela
- Functional Neuromodulation and Novel Therapeutics Laboratory, Asia Pacific Centre for Neuromodulation, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia
| | - Suelen L Boschen
- Department of Neurologic Surgery, Neural Engineering Laboratories, Mayo Clinic, Rochester, Minnesota, USA
- Department of Neurologic Surgery, Applied Computational Neurophysiology and Neuromodulation Laboratory, Mayo Clinic, Rochester, Minnesota, USA
| | - Nathanael Yates
- Functional Neuromodulation and Novel Therapeutics Laboratory, Asia Pacific Centre for Neuromodulation, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia
| | - Tristan Houghton
- Functional Neuromodulation and Novel Therapeutics Laboratory, Asia Pacific Centre for Neuromodulation, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia
| | - Charles D Blaha
- Department of Neurologic Surgery, Neural Engineering Laboratories, Mayo Clinic, Rochester, Minnesota, USA
| | - Kendall H Lee
- Department of Neurologic Surgery, Neural Engineering Laboratories, Mayo Clinic, Rochester, Minnesota, USA
| | - Kevin E Bennet
- Department of Neurologic Surgery, Neural Engineering Laboratories, Mayo Clinic, Rochester, Minnesota, USA
- Division of Engineering, Mayo Clinic, Rochester, Minnesota, USA
| | - Abbas Z Kouzani
- School of Engineering, Deakin University, Geelong, Victoria, Australia
| | - Michael Berk
- School of Medicine, IMPACT-The Institute for Mental and Physical Health and Clinical Translation, Barwon Health, Deakin University, Geelong, Victoria, Australia
| | - João Quevedo
- Faillace Department of Psychiatry and Behavioral Sciences, Center for Interventional Psychiatry, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth Houston), Houston, Texas, USA
- Faillace Department of Psychiatry and Behavioral Sciences, Center of Excellence on Mood Disorders, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, Texas, USA
- Faillace Department of Psychiatry and Behavioral Sciences, Translational Psychiatry Program, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, Texas, USA
- Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Santa Catarina, Brazil
| | - Samira S Valvassori
- Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Santa Catarina, Brazil
| | - Susannah J Tye
- Functional Neuromodulation and Novel Therapeutics Laboratory, Asia Pacific Centre for Neuromodulation, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia
- Department of Psychiatry and Psychology, Translational Neuroscience Laboratory, Mayo Clinic, Rochester, Minnesota, USA
- Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota, USA
- Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia, USA
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19
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Meinke C, Lueken U, Walter H, Hilbert K. Predicting treatment outcome based on resting-state functional connectivity in internalizing mental disorders: A systematic review and meta-analysis. Neurosci Biobehav Rev 2024; 160:105640. [PMID: 38548002 DOI: 10.1016/j.neubiorev.2024.105640] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 02/29/2024] [Accepted: 03/21/2024] [Indexed: 04/07/2024]
Abstract
Predicting treatment outcome in internalizing mental disorders prior to treatment initiation is pivotal for precision mental healthcare. In this regard, resting-state functional connectivity (rs-FC) and machine learning have often shown promising prediction accuracies. This systematic review and meta-analysis evaluates these studies, considering their risk of bias through the Prediction Model Study Risk of Bias Assessment Tool (PROBAST). We examined the predictive performance of features derived from rs-FC, identified features with the highest predictive value, and assessed the employed machine learning pipelines. We searched the electronic databases Scopus, PubMed and PsycINFO on the 12th of December 2022, which resulted in 13 included studies. The mean balanced accuracy for predicting treatment outcome was 77% (95% CI: [72%- 83%]). rs-FC of the dorsolateral prefrontal cortex had high predictive value in most studies. However, a high risk of bias was identified in all studies, compromising interpretability. Methodological recommendations are provided based on a comprehensive exploration of the studies' machine learning pipelines, and potential fruitful developments are discussed.
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Affiliation(s)
- Charlotte Meinke
- Department of Psychology, Humboldt-Universität zu Berlin, Germany.
| | - Ulrike Lueken
- Department of Psychology, Humboldt-Universität zu Berlin, Germany; German Center for Mental Health (DZPG), partner site Berlin/Potsdam, Germany.
| | - Henrik Walter
- Charité Universtätsmedizin Berlin, corporate member of FU Berlin and Humboldt Universität zu Berlin, Department of Psychiatrie and Psychotherapy, CCM, Germany.
| | - Kevin Hilbert
- Department of Psychology, Humboldt-Universität zu Berlin, Germany; Department of Psychology, Health and Medical University Erfurt, Germany.
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20
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Leserri S, Segura-Amil A, Nowacki A, Debove I, Petermann K, Schäppi L, Preti MG, Van De Ville D, Pollo C, Walther S, Nguyen TAK. Linking connectivity of deep brain stimulation of nucleus accumbens area with clinical depression improvements: a retrospective longitudinal case series. Eur Arch Psychiatry Clin Neurosci 2024; 274:685-696. [PMID: 37668723 PMCID: PMC10994999 DOI: 10.1007/s00406-023-01683-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 08/14/2023] [Indexed: 09/06/2023]
Abstract
Treatment-resistant depression is a severe form of major depressive disorder and deep brain stimulation is currently an investigational treatment. The stimulation's therapeutic effect may be explained through the functional and structural connectivities between the stimulated area and other brain regions, or to depression-associated networks. In this longitudinal, retrospective study, four female patients with treatment-resistant depression were implanted for stimulation in the nucleus accumbens area at our center. We analyzed the structural and functional connectivity of the stimulation area: the structural connectivity was investigated with probabilistic tractography; the functional connectivity was estimated by combining patient-specific stimulation volumes and a normative functional connectome. These structural and functional connectivity profiles were then related to four clinical outcome scores. At 1-year follow-up, the remission rate was 66%. We observed a consistent structural connectivity to Brodmann area 25 in the patient with the longest remission phase. The functional connectivity analysis resulted in patient-specific R-maps describing brain areas significantly correlated with symptom improvement in this patient, notably the prefrontal cortex. But the connectivity analysis was mixed across patients, calling for confirmation in a larger cohort and over longer time periods.
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Affiliation(s)
- Simona Leserri
- Department of Neurosurgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- ARTORG Center for Biomedical Engineering Research, University Bern, Bern, Switzerland
- Neuro-X Institute, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
| | - Alba Segura-Amil
- Department of Neurosurgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- ARTORG Center for Biomedical Engineering Research, University Bern, Bern, Switzerland
| | - Andreas Nowacki
- Department of Neurosurgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Ines Debove
- Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Katrin Petermann
- Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Lea Schäppi
- Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland
| | - Maria Giulia Preti
- Neuro-X Institute, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
- CIBM Center for Biomedical Imaging, Lausanne, Switzerland
- Department of Radiology and Medical InformaticsFaculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Dimitri Van De Ville
- Neuro-X Institute, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
- CIBM Center for Biomedical Imaging, Lausanne, Switzerland
- Department of Radiology and Medical InformaticsFaculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Claudio Pollo
- Department of Neurosurgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Sebastian Walther
- Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland
| | - T A Khoa Nguyen
- Department of Neurosurgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
- ARTORG Center for Biomedical Engineering Research, University Bern, Bern, Switzerland.
- ARTORG IGT, Murtenstrasse 50, 3008, Bern, Switzerland.
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21
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Ranjan M, Mahoney JJ, Rezai AR. Neurosurgical neuromodulation therapy for psychiatric disorders. Neurotherapeutics 2024; 21:e00366. [PMID: 38688105 PMCID: PMC11070709 DOI: 10.1016/j.neurot.2024.e00366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 04/09/2024] [Accepted: 04/16/2024] [Indexed: 05/02/2024] Open
Abstract
Psychiatric disorders are among the leading contributors to global disease burden and disability. A significant portion of patients with psychiatric disorders remain treatment-refractory to best available therapy. With insights from the neurocircuitry of psychiatric disorders and extensive experience of neuromodulation with deep brain stimulation (DBS) in movement disorders, DBS is increasingly being considered to modulate the neural network in psychiatric disorders. Currently, obsessive-compulsive disorder (OCD) is the only U.S. FDA (United States Food and Drug Administration) approved DBS indication for psychiatric disorders. Medically refractory depression, addiction, and other psychiatric disorders are being explored for DBS neuromodulation. Studies evaluating DBS for psychiatric disorders are promising but lack larger, controlled studies. This paper presents a brief review and the current state of DBS and other neurosurgical neuromodulation therapies for OCD and other psychiatric disorders. We also present a brief review of MR-guided Focused Ultrasound (MRgFUS), a novel form of neurosurgical neuromodulation, which can target deep subcortical structures similar to DBS, but in a noninvasive fashion. Early experiences of neurosurgical neuromodulation therapies, including MRgFUS neuromodulation are encouraging in psychiatric disorders; however, they remain investigational. Currently, DBS and VNS are the only FDA approved neurosurgical neuromodulation options in properly selected cases of OCD and depression, respectively.
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Affiliation(s)
- Manish Ranjan
- Department of Neurosurgery, WVU Rockefeller Neuroscience Institute, Morgantown, WV, USA.
| | - James J Mahoney
- Department of Behavioral Medicine and Psychiatry, WVU Rockefeller Neuroscience Institute, Morgantown, WV, USA; Department of Neuroscience, WVU Rockefeller Neuroscience Institute, Morgantown, WV, USA
| | - Ali R Rezai
- Department of Neurosurgery, WVU Rockefeller Neuroscience Institute, Morgantown, WV, USA; Department of Neuroscience, WVU Rockefeller Neuroscience Institute, Morgantown, WV, USA
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22
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Valentim WL, Tylee DS, Polimanti R. A perspective on translating genomic discoveries into targets for brain-machine interface and deep brain stimulation devices. WIREs Mech Dis 2024; 16:e1635. [PMID: 38059513 PMCID: PMC11163995 DOI: 10.1002/wsbm.1635] [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: 03/20/2023] [Revised: 10/22/2023] [Accepted: 11/17/2023] [Indexed: 12/08/2023]
Abstract
Mental illnesses have a huge impact on individuals, families, and society, so there is a growing need for more efficient treatments. In this context, brain-computer interface (BCI) technology has the potential to revolutionize the options for neuropsychiatric therapies. However, the development of BCI-based therapies faces enormous challenges, such as power dissipation constraints, lack of credible feedback mechanisms, uncertainty of which brain areas and frequencies to target, and even which patients to treat. Some of these setbacks are due to the large gap in our understanding of brain function. In recent years, large-scale genomic analyses uncovered an unprecedented amount of information regarding the biology of the altered brain function observed across the psychopathology spectrum. We believe findings from genetic studies can be useful to refine BCI technology to develop novel treatment options for mental illnesses. Here, we assess the latest advancements in both fields, the possibilities that can be generated from their intersection, and the challenges that these research areas will need to address to ensure that translational efforts can lead to effective and reliable interventions. Specifically, starting from highlighting the overlap between mechanisms uncovered by large-scale genetic studies and the current targets of deep brain stimulation treatments, we describe the steps that could help to translate genomic discoveries into BCI targets. Because these two research areas have not been previously presented together, the present article can provide a novel perspective for scientists with different research backgrounds. This article is categorized under: Neurological Diseases > Genetics/Genomics/Epigenetics Neurological Diseases > Biomedical Engineering.
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Affiliation(s)
- Wander L. Valentim
- Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT
| | - Daniel S. Tylee
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT
- VA CT Healthcare Center, West Haven, CT, USA
| | - Renato Polimanti
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT
- VA CT Healthcare Center, West Haven, CT, USA
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23
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Zhang J, Wu X, Si Y, Liu Y, Wang X, Geng Y, Chang Q, Jiang X, Zhang H. Abnormal caudate nucleus activity in patients with depressive disorder: Meta-analysis of task-based functional magnetic resonance imaging studies with behavioral domain. Psychiatry Res Neuroimaging 2024; 338:111769. [PMID: 38141592 DOI: 10.1016/j.pscychresns.2023.111769] [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: 11/30/2022] [Revised: 11/17/2023] [Accepted: 11/26/2023] [Indexed: 12/25/2023]
Abstract
During task-based functional magnetic resonance imaging (t-fMRI) patients with depressive disorder (DD) have shown abnormal caudate nucleus activation. There have been no meta-analyses that are conducted on the caudate nucleus using Activation Likelihood Estimation (ALE) in patients with DD, and the relationships between abnormal caudate activity and different behavior domains in patients with DD remain unclear. There were 24 previously published t-fMRI studies included in the study with the caudate nucleus as the region of interest. Meta-analyses were performed using the method of ALE. Included five ALE meta-analyses: (1) the hypoactivated caudate nucleus relative to healthy controls (HCs); (2) the hyper-activated caudate nucleus; (3) the abnormal activation in the caudate nucleus in the emotion domain; (4) the abnormal activation in cognition domain; (5) the abnormal activation in the affective cognition domain. Results revealed that the hypo-/hyper-activity in the caudate subregions is mainly located in the caudate body and head, while the relationships between abnormal caudate subregions and different behavior domains are complex. The hypoactivation of the caudate body and head plays a key role in the emotions which indicates there is a positive relationship between the decreased caudate activity and depressed emotional behaviors in patients with DD.
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Affiliation(s)
- Jiajia Zhang
- Department of Psychology, Xinxiang Medical University, Henan 453003, PR China; Xinxiang Key Laboratory of Psychopathology and Cognitive Neuroscience, Xinxiang, 453003, PR China; Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453002, PR China
| | - Xin Wu
- Department of Psychology, Xinxiang Medical University, Henan 453003, PR China; Xinxiang Key Laboratory of Psychopathology and Cognitive Neuroscience, Xinxiang, 453003, PR China
| | - Yajing Si
- Department of Psychology, Xinxiang Medical University, Henan 453003, PR China; Xinxiang Key Laboratory of Psychopathology and Cognitive Neuroscience, Xinxiang, 453003, PR China
| | - Yahui Liu
- Department of Psychology, Xinxiang Medical University, Henan 453003, PR China; Xinxiang Key Laboratory of Psychopathology and Cognitive Neuroscience, Xinxiang, 453003, PR China
| | - Xueke Wang
- Department of Psychology, Xinxiang Medical University, Henan 453003, PR China; Xinxiang Key Laboratory of Psychopathology and Cognitive Neuroscience, Xinxiang, 453003, PR China; Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453002, PR China
| | - Yibo Geng
- Department of Radiology, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, PR China
| | - Qiaohua Chang
- Department of Nursing, Xinxiang Medical University, Henan 453003, PR China
| | - Xiaoxiao Jiang
- Department of Nursing, Xinxiang Medical University, Henan 453003, PR China
| | - Hongxing Zhang
- Department of Psychology, Xinxiang Medical University, Henan 453003, PR China; Xinxiang Key Laboratory of Psychopathology and Cognitive Neuroscience, Xinxiang, 453003, PR China; Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453002, PR China.
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24
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Kilian HM, Schiller B, Meyer-Doll DM, Heinrichs M, Schläpfer TE. Normalized affective responsiveness following deep brain stimulation of the medial forebrain bundle in depression. Transl Psychiatry 2024; 14:6. [PMID: 38191528 PMCID: PMC10774255 DOI: 10.1038/s41398-023-02712-y] [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: 03/12/2023] [Revised: 12/06/2023] [Accepted: 12/12/2023] [Indexed: 01/10/2024] Open
Abstract
Deep brain stimulation (DBS) of the supero-lateral medial forebrain bundle (slMFB) is associated with rapid and sustained antidepressant effects in treatment-resistant depression (TRD). Beyond that, improvements in social functioning have been reported. However, it is unclear whether social skills, the basis of successful social functioning, are systematically altered following slMFB DBS. Therefore, the current study investigated specific social skills (affective empathy, compassion, and theory of mind) in patients with TRD undergoing slMFB DBS in comparison to healthy subjects. 12 patients with TRD and 12 age- and gender-matched healthy subjects (5 females) performed the EmpaToM, a video-based naturalistic paradigm differentiating between affective empathy, compassion, and theory of mind. Patients were assessed before and three months after DBS onset and compared to an age- and gender-matched sample of healthy controls. All data were analyzed using non-parametric Mann-Whitney U tests. DBS treatment significantly affected patients' affective responsiveness towards emotional versus neutral situations (i.e. affective empathy): While their affective responsiveness was reduced compared to healthy subjects at baseline, they showed normalized affective responsiveness three months after slMFB DBS onset. No effects occurred in other domains with persisting deficits in compassion and intact socio-cognitive skills. Active slMFB DBS resulted in a normalized affective responsiveness in patients with TRD. This specific effect might represent one factor supporting the resumption of social activities after recovery from chronic depression. Considering the small size of this unique sample as well as the explorative nature of this study, future studies are needed to investigate the robustness of these effects.
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Affiliation(s)
- Hannah Marlene Kilian
- Division of Interventional Biological Psychiatry, Department of Psychiatry and Psychotherapy Medical Center - University of Freiburg, Faculty of Medicine, DE-79104, Freiburg, Germany.
| | - Bastian Schiller
- Department of Psychology, Laboratory for Biological Psychology, Clinical Psychology and Psychotherapy, University of Freiburg, DE-79104, Freiburg, Germany
| | - Dora Margarete Meyer-Doll
- Division of Interventional Biological Psychiatry, Department of Psychiatry and Psychotherapy Medical Center - University of Freiburg, Faculty of Medicine, DE-79104, Freiburg, Germany
| | - Markus Heinrichs
- Department of Psychology, Laboratory for Biological Psychology, Clinical Psychology and Psychotherapy, University of Freiburg, DE-79104, Freiburg, Germany
| | - Thomas Eduard Schläpfer
- Division of Interventional Biological Psychiatry, Department of Psychiatry and Psychotherapy Medical Center - University of Freiburg, Faculty of Medicine, DE-79104, Freiburg, Germany
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25
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Sellers KK, Cohen JL, Khambhati AN, Fan JM, Lee AM, Chang EF, Krystal AD. Closed-loop neurostimulation for the treatment of psychiatric disorders. Neuropsychopharmacology 2024; 49:163-178. [PMID: 37369777 PMCID: PMC10700557 DOI: 10.1038/s41386-023-01631-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 05/31/2023] [Accepted: 06/02/2023] [Indexed: 06/29/2023]
Abstract
Despite increasing prevalence and huge personal and societal burden, psychiatric diseases still lack treatments which can control symptoms for a large fraction of patients. Increasing insight into the neurobiology underlying these diseases has demonstrated wide-ranging aberrant activity and functioning in multiple brain circuits and networks. Together with varied presentation and symptoms, this makes one-size-fits-all treatment a challenge. There has been a resurgence of interest in the use of neurostimulation as a treatment for psychiatric diseases. Initial studies using continuous open-loop stimulation, in which clinicians adjusted stimulation parameters during patient visits, showed promise but also mixed results. Given the periodic nature and fluctuations of symptoms often observed in psychiatric illnesses, the use of device-driven closed-loop stimulation may provide more effective therapy. The use of a biomarker, which is correlated with specific symptoms, to deliver stimulation only during symptomatic periods allows for the personalized therapy needed for such heterogeneous disorders. Here, we provide the reader with background motivating the use of closed-loop neurostimulation for the treatment of psychiatric disorders. We review foundational studies of open- and closed-loop neurostimulation for neuropsychiatric indications, focusing on deep brain stimulation, and discuss key considerations when designing and implementing closed-loop neurostimulation.
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Affiliation(s)
- Kristin K Sellers
- Department of Neurological Surgery, University of California, San Francisco, CA, USA
- Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
| | - Joshua L Cohen
- Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
- Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA
| | - Ankit N Khambhati
- Department of Neurological Surgery, University of California, San Francisco, CA, USA
- Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
| | - Joline M Fan
- Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
- Department of Neurology, University of California, San Francisco, CA, USA
| | - A Moses Lee
- Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
- Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA
| | - Edward F Chang
- Department of Neurological Surgery, University of California, San Francisco, CA, USA
- Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
| | - Andrew D Krystal
- Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
- Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA.
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Persad AR, Coote NR, Waterhouse K, McLeod S, Norton JA, Gould L, Vitali AM. Medial forebrain bundle stimulation after failed subcallosal cingulate deep brain stimulation for treatment-resistant depression: Efficacy of a dual deep brain stimulation system for depression. Brain Stimul 2024; 17:68-70. [PMID: 38159905 DOI: 10.1016/j.brs.2023.12.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 12/26/2023] [Indexed: 01/03/2024] Open
Affiliation(s)
- Amit R Persad
- Department of Neurological Surgery, Stanford University, Stanford, CA, USA
| | - Nicole R Coote
- Division of Neurosurgery, Department of Surgery, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Karen Waterhouse
- Division of Neurosurgery, Department of Surgery, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Sara McLeod
- Division of Neurosurgery, Department of Surgery, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Jonathan A Norton
- Division of Neurosurgery, Department of Surgery, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Layla Gould
- Division of Neurosurgery, Department of Surgery, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Aleksander M Vitali
- Division of Neurosurgery, Department of Surgery, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
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Metzger BA, Kalva P, Mocchi MM, Cui B, Adkinson JA, Wang Z, Mathura R, Kanja K, Gavvala J, Krishnan V, Lin L, Maheshwari A, Shofty B, Magnotti JF, Willie JT, Sheth SA, Bijanki KR. Intracranial stimulation and EEG feature analysis reveal affective salience network specialization. Brain 2023; 146:4366-4377. [PMID: 37293814 PMCID: PMC10545499 DOI: 10.1093/brain/awad200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 05/04/2023] [Accepted: 05/11/2023] [Indexed: 06/10/2023] Open
Abstract
Emotion is represented in limbic and prefrontal brain areas, herein termed the affective salience network (ASN). Within the ASN, there are substantial unknowns about how valence and emotional intensity are processed-specifically, which nodes are associated with affective bias (a phenomenon in which participants interpret emotions in a manner consistent with their own mood). A recently developed feature detection approach ('specparam') was used to select dominant spectral features from human intracranial electrophysiological data, revealing affective specialization within specific nodes of the ASN. Spectral analysis of dominant features at the channel level suggests that dorsal anterior cingulate (dACC), anterior insula and ventral-medial prefrontal cortex (vmPFC) are sensitive to valence and intensity, while the amygdala is primarily sensitive to intensity. Akaike information criterion model comparisons corroborated the spectral analysis findings, suggesting all four nodes are more sensitive to intensity compared to valence. The data also revealed that activity in dACC and vmPFC were predictive of the extent of affective bias in the ratings of facial expressions-a proxy measure of instantaneous mood. To examine causality of the dACC in affective experience, 130 Hz continuous stimulation was applied to dACC while patients viewed and rated emotional faces. Faces were rated significantly happier during stimulation, even after accounting for differences in baseline ratings. Together the data suggest a causal role for dACC during the processing of external affective stimuli.
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Affiliation(s)
- Brian A Metzger
- Department of Psychology, Swarthmore College, Swarthmore, PA 19081, USA
| | - Prathik Kalva
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030, USA
| | - Madaline M Mocchi
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030, USA
| | - Brian Cui
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030, USA
| | - Joshua A Adkinson
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030, USA
| | - Zhengjia Wang
- Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Raissa Mathura
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030, USA
| | - Kourtney Kanja
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030, USA
| | - Jay Gavvala
- Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA
| | - Vaishnav Krishnan
- Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA
| | - Lu Lin
- Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA
| | - Atul Maheshwari
- Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA
| | - Ben Shofty
- Department of Neurosurgery, University of Utah Health, Salt Lake City, UT 84132, USA
| | - John F Magnotti
- Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Jon T Willie
- Department of Neurosurgery, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA
| | - Sameer A Sheth
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030, USA
| | - Kelly R Bijanki
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030, USA
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Wivatvongvana P, Soonthornthum C, Kitisak K. Intermittent tetraburst stimulation combined with transcranial direct current stimulation once weekly for treatment-resistant depression: a case report. J Med Case Rep 2023; 17:415. [PMID: 37779185 PMCID: PMC10544463 DOI: 10.1186/s13256-023-04152-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 08/30/2023] [Indexed: 10/03/2023] Open
Abstract
BACKGROUND Single-time non-invasive brain stimulation was carried out using the two-technique approach on a patient suffering from treatment-resistant depression. Five treatment sessions given at weekly intervals resulted in a significant improvement in the Patient Health Questionnaire-9 score for up to 6 weeks. The findings of this study could pave the way for a more efficient less resource-intensive time- and budget-saving technique of employing non-invasive brain stimulation for patients with treatment-resistant depression by minimizing the number of stimulation sessions. CASE PRESENTATION A 67-year-old married non-Latino white American woman suffering from treatment-resistant depression received intermittent tetraburst stimulation in combination with transcranial direct current stimulation weekly for 5 consecutive weeks. Diagnostic transcranial magnetic stimulation showed an observable electrophysiological change. The patient reported a drastic improvement in Patient Health Questionnaire-9 score up until 6-week follow-up and expressed satisfaction with the treatment. CONCLUSIONS This case study suggests that a streamlined protocol for using non-invasive brain stimulation could prove more effective for patients and healthcare providers in terms of safety in comparison to the present guidelines.
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Affiliation(s)
- Pakorn Wivatvongvana
- Department of Rehabilitation Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
| | - Chutimon Soonthornthum
- Department of Rehabilitation Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Kittipong Kitisak
- Department of Rehabilitation Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
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29
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Pelliccia V, Del Vecchio M, Avanzini P, Revay M, Sartori I, Caruana F. 70 Years of Human Cingulate Cortex Stimulation. Functions and Dysfunctions Through the Lens of Electrical Stimulation. J Clin Neurophysiol 2023; 40:491-500. [PMID: 36007014 DOI: 10.1097/wnp.0000000000000961] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
SUMMARY In this review, we retrace the results of 70 years of human cingulate cortex (CC) intracerebral electrical stimulation and discuss its contribution to our understanding of the anatomofunctional and clinical aspects of this wide cortical region. The review is divided into three main sections. In the first section, we report the results obtained by the stimulation of the anterior, middle, and posterior CC, in 30 studies conducted on approximately 1,000 patients from the 1950s to the present day. These studies show that specific manifestations can be reliably associated with specific cingulate subfields, with autonomic, interoceptive, and emotional manifestations clustered in the anterior cingulate, goal-oriented motor behaviors elicited from the anterior midcingulate and a variety of sensory symptoms characterizing the posterior cingulate regions. In the second section, we compare the effect of CC intracerebral electrical stimulation with signs and manifestations characterizing cingulate epilepsy, showing that the stimulation mapping of CC subfields provides precious information for understanding cingulate epileptic manifestations. The last section tackles the issue of the discrepancy emerging when comparing the results of clinical (electrical stimulation, epilepsy) studies-revealing the quintessential affective and motor nature of the CC-with that reported by neuroimaging studies-which focus on high-level cognitive functions. Particular attention will be paid to the hypothesis that CC hosts a "Pain Matrix" specifically involved in pain perception, which we will discuss in the light of the fact that the stimulation of CC (as well as cingulate epileptic seizures) does not induce nociceptive effects.
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Affiliation(s)
- Veronica Pelliccia
- "Claudio Munari" Epilepsy Surgery Center, ASST GOM Niguarda, Milano, Italy; and
| | - Maria Del Vecchio
- Institute of Neuroscience, National Research Council of Italy (CNR), Parma, Italy
| | - Pietro Avanzini
- Institute of Neuroscience, National Research Council of Italy (CNR), Parma, Italy
| | - Martina Revay
- "Claudio Munari" Epilepsy Surgery Center, ASST GOM Niguarda, Milano, Italy; and
| | - Ivana Sartori
- "Claudio Munari" Epilepsy Surgery Center, ASST GOM Niguarda, Milano, Italy; and
| | - Fausto Caruana
- Institute of Neuroscience, National Research Council of Italy (CNR), Parma, Italy
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Wang L, Li J, Pan Y, Huang P, Li D, Voon V. Subacute alpha frequency (10Hz) subthalamic stimulation for emotional processing in Parkinson's disease. Brain Stimul 2023; 16:1223-1231. [PMID: 37567462 DOI: 10.1016/j.brs.2023.08.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 05/21/2023] [Accepted: 08/07/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Psychiatric comorbidities are common in Parkinson's disease (PD) and may change with high-frequency stimulation targeting the subthalamic nucleus. Numerous accounts indicate subthalamic alpha-frequency oscillation is implicated in emotional processing. While intermittent alpha-frequency (10Hz) stimulation induces positive emotional effects, with more ventromedial contacts inducing larger effects, little is known about the subacute effect of ventral 10Hz subthalamic stimulation on emotional processing. OBJECTIVE/HYPOTHESIS To evaluate the subacute effect of 10Hz stimulation at bilateral ventral subthalamic nucleus on emotional processing in PD patients using an affective task, compared to that of clinical-frequency stimulation and off-stimulation. METHODS Twenty PD patients with bilateral subthalamic deep brain stimulation for more than six months were tested with the affective task under three stimulation conditions (10Hz, 130Hz, and off-stimulation) in a double-blinded randomized design. RESULTS While 130Hz stimulation reduced arousal ratings in all patients, 10Hz stimulation increased arousal selectively in patients with higher depression scores. Furthermore, 10Hz stimulation induced a positive shift in valence rating to negative emotional stimuli in patients with lower apathy scores, and 130Hz stimulation led to more positive valence to emotional stimuli in the patients with higher apathy scores. Notably, we found correlational relationships between stimulation site and affective rating: arousal ratings increase with stimulation from anterior to posterior site, and positive valence ratings increase with stimulation from dorsal to ventral site of the ventral subthalamic nucleus. CONCLUSIONS Our findings highlight the distinctive role of 10Hz stimulation on subjective emotional experience and unveil the spatial organization of the stimulation effect.
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Affiliation(s)
- Linbin Wang
- Institute of Science and Technology for Brain-Inspired Intelligence (ISTBI), Fudan University, Shanghai, China; Department of Neurosurgery, Center for Functional Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jun Li
- School of Information Science and Technology, ShanghaiTech University, Shanghai, China
| | - Yixin Pan
- Department of Neurosurgery, Center for Functional Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Peng Huang
- Department of Neurosurgery, Center for Functional Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Dianyou Li
- Department of Neurosurgery, Center for Functional Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Valerie Voon
- Institute of Science and Technology for Brain-Inspired Intelligence (ISTBI), Fudan University, Shanghai, China; Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
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Li SJ, Lo YC, Tseng HY, Lin SH, Kuo CH, Chen TC, Chang CW, Liang YW, Lin YC, Wang CY, Cho TY, Wang MH, Chen CT, Chen YY. Nucleus accumbens deep brain stimulation improves depressive-like behaviors through BDNF-mediated alterations in brain functional connectivity of dopaminergic pathway. Neurobiol Stress 2023; 26:100566. [PMID: 37664874 PMCID: PMC10474237 DOI: 10.1016/j.ynstr.2023.100566] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 08/14/2023] [Accepted: 08/19/2023] [Indexed: 09/05/2023] Open
Abstract
Major depressive disorder (MDD), a common psychiatric condition, adversely affects patients' moods and quality of life. Despite the development of various treatments, many patients with MDD remain vulnerable and inadequately controlled. Since anhedonia is a feature of depression and there is evidence of leading to metabolic disorder, deep brain stimulation (DBS) to the nucleus accumbens (NAc) might be promising in modulating the dopaminergic pathway. To determine whether NAc-DBS alters glucose metabolism via mitochondrial alteration and neurogenesis and whether these changes increase neural plasticity that improves behavioral functions in a chronic social defeat stress (CSDS) mouse model. The Lab-designed MR-compatible neural probes were implanted in the bilateral NAc of C57BL/6 mice with and without CSDS, followed by DBS or sham stimulation. All animals underwent open-field and sucrose preference testing, and brain resting-state functional MRI analysis. Meanwhile, we checked the placement of neural probes in each mouse by T2 images. By confirming the placement location, mice with incorrect probe placement (the negative control group) showed no significant therapeutic effects in behavioral performance and functional connectivity (FC) after receiving electrical stimulation and were excluded from further analysis. Western blotting, seahorse metabolic analysis, and electron microscopy were further applied for the investigation of NAc-DBS. We found NAc-DBS restored emotional deficits in CSDS-subjected mice. Concurrent with behavioral amelioration, the CSDS DBS-on group exhibited enhanced FC in the dopaminergic pathway with increased expression of BDNF- and NeuN-positive cells increased dopamine D1 receptor, dopamine D2 receptors, and TH in the medial prefrontal cortex, NAc, ventral hippocampus, ventral tegmental area, and amygdala. Increased pAMPK/total AMPK and PGC-1α levels, functions of oxidative phosphorylation, and mitochondrial biogenesis were also observed after NAc-DBS treatment. Our findings demonstrate that NAc-DBS can promote BDNF expression, which alters FC and metabolic profile in the dopaminergic pathway, suggesting a potential strategy for ameliorating emotional processes in individuals with MDD.
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Affiliation(s)
- Ssu-Ju Li
- Department of Biomedical Engineering, National Yang Ming Chiao Tung University, No.155, Sec. 2, Linong St., Taipei, 112304, Taiwan, ROC
| | - Yu-Chun Lo
- The Ph.D. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University, No. 250 Wu-Xing St., Taipei, 11031, Taiwan, ROC
| | - Hsin-Yi Tseng
- The Ph.D. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University and National Health Research Institutes, Taipei, 11031, Taiwan, ROC
| | - Sheng-Huang Lin
- Department of Neurology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 707, Sec. 3, Zhongyang Rd., Hualien, 97002, Taiwan, ROC
- Department of Neurology, School of Medicine, Tzu Chi University, No. 701, Sec. 3, Zhongyang Rd., Hualien, 97004, Taiwan, ROC
| | - Chao-Hung Kuo
- Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Taipei, 11217, Taiwan, ROC
| | - Ting-Chieh Chen
- Department of Biomedical Engineering, National Yang Ming Chiao Tung University, No.155, Sec. 2, Linong St., Taipei, 112304, Taiwan, ROC
| | - Ching-Wen Chang
- Department of Biomedical Engineering, National Yang Ming Chiao Tung University, No.155, Sec. 2, Linong St., Taipei, 112304, Taiwan, ROC
- Institute of Biomedical Sciences, Academia Sinica, No. 128, Sec. 2, Academia Rd., Taipei, 115024, Taiwan
| | - Yao-Wen Liang
- Department of Biomedical Engineering, National Yang Ming Chiao Tung University, No.155, Sec. 2, Linong St., Taipei, 112304, Taiwan, ROC
| | - Yi-Chen Lin
- Department of Biomedical Engineering, National Yang Ming Chiao Tung University, No.155, Sec. 2, Linong St., Taipei, 112304, Taiwan, ROC
| | - Chih-Yu Wang
- Department of Biomedical Engineering, National Yang Ming Chiao Tung University, No.155, Sec. 2, Linong St., Taipei, 112304, Taiwan, ROC
| | - Tsai-Yu Cho
- Department of Biomedical Engineering, National Yang Ming Chiao Tung University, No.155, Sec. 2, Linong St., Taipei, 112304, Taiwan, ROC
| | - Mu-Hua Wang
- Department of Biomedical Engineering, National Yang Ming Chiao Tung University, No.155, Sec. 2, Linong St., Taipei, 112304, Taiwan, ROC
| | - Ching-Te Chen
- Abbott Medical Taiwan Co, 5/F No. 407, Ruei-Guang Rd., Taipei, 11492, Taiwan, ROC
| | - You-Yin Chen
- Department of Biomedical Engineering, National Yang Ming Chiao Tung University, No.155, Sec. 2, Linong St., Taipei, 112304, Taiwan, ROC
- The Ph.D. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University, No. 250 Wu-Xing St., Taipei, 11031, Taiwan, ROC
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Shuto Y, Walinda E, Morimoto D, Sugase K. Conformational Fluctuations and Induced Orientation of a Protein, Its Solvation Shell, and Bulk Water in Weak Non-Unfolding External Electric Fields. J Phys Chem B 2023; 127:7417-7430. [PMID: 37587419 DOI: 10.1021/acs.jpcb.3c01683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/18/2023]
Abstract
Extreme external electric fields have been reported to disrupt the tertiary structure of stably folded proteins; however, the effects of weaker electric fields on many biomolecules, especially net-uncharged proteins, and on the surrounding aqueous environment have been rarely discussed. To explore these effects at the atomic level, here, we have used molecular dynamics simulations to estimate rotational motion and induced structural fluctuations in the model protein ubiquitin and its hydration layer due to applied non-unfolding electrostatic fields. When exposed to weak electric fields of up to 0.2 V nm-1, ubiquitin displayed competition between internal structure-maintaining molecular interactions and the external orienting force, which disrupted the local structure in certain regions of the protein. Moreover, relative to hydration water, bulk water showed a greater tendency to align with the electric field, indicating that the presence of protein caused hydration water to acquire rotational mobility different from that in a pure-water system. The differential influence of the applied electric field on the hydration and bulk water surrounding ubiquitin will be common to almost all (nonmembrane) biomacromolecules. Our findings highlight the importance of local dipoles and their electric polarizability even in net-uncharged biomolecules.
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Affiliation(s)
- Yusuke Shuto
- Graduate School of Agriculture, Kyoto University, N346 Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan
| | - Erik Walinda
- Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
| | - Daichi Morimoto
- Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Kyoto-Daigaku Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
| | - Kenji Sugase
- Graduate School of Agriculture, Kyoto University, N346 Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan
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Iess G, Bonomo G, Levi V, Aquino D, Zekaj E, Mezza F, Servello D. MER and increased operative time are not risk factors for the formation of pneumocephalus during DBS. Sci Rep 2023; 13:9324. [PMID: 37291256 PMCID: PMC10250399 DOI: 10.1038/s41598-023-30289-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Accepted: 02/21/2023] [Indexed: 06/10/2023] Open
Abstract
Although only recently directional leads have proven their potential to compensate for sub-optimally placed electrodes, optimal lead positioning remains the most critical factor in determining Deep Brain Stimulation (DBS) outcome. Pneumocephalus is a recognized source of error, but the factors that contribute to its formation are still a matter of debate. Among these, operative time is one of the most controversial. Because cases of DBS performed with Microelectrode Recordings (MER) are affected by an increase in surgical length, it is useful to analyze whether MER places patients at risk for increased intracranial air entry. Data of 94 patients from two different institutes who underwent DBS for different neurologic and psychiatric conditions were analyzed for the presence of postoperative pneumocephalus. Operative time and use of MER, as well as other potential risk factors for pneumocephalus (age, awake vs. asleep surgery, number of MER passages, burr hole size, target and unilateral vs. bilateral implants) were examined. Mann-Whitney U and Kruskal-Wallis tests were utilized to compare intracranial air distributions across groups of categorical variables. Partial correlations were used to assess the association between time and volume. A generalized linear model was created to predict the effects of time and MER on the volume of intracranial air, controlling for other potential risk factors identified: age, number of MER passages, awake vs. asleep surgery, burr hole size, target, unilateral vs. bilateral surgery. Significantly different distributions of air volume were noted between different targets, unilateral vs. bilateral implants, and number of MER trajectories. Patients undergoing DBS with MER did not present a significant increase in pneumocephalus compared to patients operated without (p = 0.067). No significant correlation was found between pneumocephalus and time. Using multivariate analysis, unilateral implants exhibited lower volumes of pneumocephalus (p = 0.002). Two specific targets exhibited significantly different volumes of pneumocephalus: the bed nucleus of the stria terminalis with lower volumes (p < 0.001) and the posterior hypothalamus with higher volumes (p = 0.011). MER, time, and other parameters analyzed failed to reach statistical significance. Operative time and use of intraoperative MER are not significant predictors of pneumocephalus during DBS. Air entry is greater for bilateral surgeries and may be also influenced by the specific stimulated target.
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Affiliation(s)
- Guglielmo Iess
- Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
- Università degli Studi di Milano, Milan, Italy.
- Department of Neurosurgery, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.
| | - Giulio Bonomo
- Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
- Università degli Studi di Milano, Milan, Italy
| | - Vincenzo Levi
- Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
| | - Domenico Aquino
- Neuroradiology Department, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
| | - Edvin Zekaj
- Department of Neurosurgery, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
| | - Federica Mezza
- Department of Economics, University of California, Los Angeles, USA
| | - Domenico Servello
- Department of Neurosurgery, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
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Paro MR, Dyrda M, Ramanan S, Wadman G, Burke SA, Cipollone I, Bosworth C, Zurek S, Senatus PB. Deep brain stimulation for movement disorders after stroke: a systematic review of the literature. J Neurosurg 2023; 138:1688-1701. [PMID: 36308482 DOI: 10.3171/2022.8.jns221334] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 08/25/2022] [Indexed: 11/06/2022]
Abstract
OBJECTIVE Stroke remains the leading cause of disability in the United States. Even as acute care for strokes advances, there are limited options for improving function once the patient reaches the subacute and chronic stages. Identification of new therapeutic approaches is critical. Deep brain stimulation (DBS) holds promise for these patients. A number of case reports and small case series have reported improvement in movement disorders after strokes in patients treated with DBS. In this systematic review, the authors have summarized the patient characteristics, anatomical targets, stimulation parameters, and outcomes of patients who have undergone DBS treatment for poststroke movement disorders. METHODS The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The PubMed, Scopus, and SpringerLink databases were searched for the keywords "DBS," "stroke," "movement," and "recovery" to identify patients treated with DBS for movement disorders after a stroke. The Joanna Briggs Institute Critical Appraisal checklists for case reports and case series were used to systematically analyze the quality of the included studies. Data collected from each study included patient demographic characteristics, stroke diagnosis, movement disorder, DBS target, stimulation parameters, complications, and outcomes. RESULTS The authors included 29 studies that described 53 patients who underwent placement of 82 total electrodes. Movement disorders included tremor (n = 18), dystonia (n = 18), hemiballism (n = 6), spastic hemiparesis (n = 1), chorea (n = 1), and mixed disorders (n = 9). The most common DBS targets were the globus pallidus internus (n = 32), ventral intermediate nucleus of thalamus (n = 25), and subthalamic area/subthalamic nucleus (n = 7). Monopolar stimulation was reported in 43 leads and bipolar stimulation in 13. High-frequency stimulation was used in 57 leads and low-frequency stimulation in 6. All patients but 1 had improvement in their movement disorders. Two complications were reported: speech impairment in 1 patient and hardware infection in another. The median (interquartile range) duration between stroke and DBS treatment was 6.5 (2.1-15.8) years. CONCLUSIONS This is the first systematic review of DBS for poststroke movement disorders. Overall, most studies to date have been case reports and small series reporting heterogeneous patients and surgical strategies. This review suggests that DBS for movement disorders after a stroke has the potential to be effective and safe for diverse patients, and DBS may be a feasible option to improve function even years after a stroke.
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Affiliation(s)
- Mitch R Paro
- 1University of Connecticut School of Medicine, Farmington
| | - Michal Dyrda
- 1University of Connecticut School of Medicine, Farmington
| | | | | | | | | | - Cory Bosworth
- 3Deep Brain Stimulation Program, Ayer Neuroscience Institute, Hartford Hospital, Hartford; and
| | - Sarah Zurek
- 3Deep Brain Stimulation Program, Ayer Neuroscience Institute, Hartford Hospital, Hartford; and
| | - Patrick B Senatus
- 3Deep Brain Stimulation Program, Ayer Neuroscience Institute, Hartford Hospital, Hartford; and
- 4Department of Neurosurgery, Hartford Hospital, Hartford, Connecticut
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35
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Orhurhu V, Hussain N, Karri J, Mariano ER, Abd-Elsayed A. Perioperative and anesthetic considerations for the management of neuromodulation systems. Reg Anesth Pain Med 2023; 48:327-336. [PMID: 37080581 DOI: 10.1136/rapm-2022-103660] [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: 03/23/2022] [Accepted: 10/04/2022] [Indexed: 04/22/2023]
Abstract
The use of neuromodulation systems is increasing for the treatment of various pathologies ranging from movement disorders to urinary incontinence to chronic pain syndromes. While the type of neuromodulation devices varies, they are largely categorized as intracranial (eg, deep brain stimulation), neuraxial (eg, spinal cord stimulation, dorsal root ganglion stimulation, and intrathecal drug delivery systems), or peripheral (eg, sacral nerve stimulation and peripheral nerve stimulation) systems. Given the increasing prevalence of these systems in the overall population, it is important for anesthesiologists, surgeons, and the perioperative healthcare team to familiarize themselves with these systems and their unique perioperative considerations. In this review, we explore and highlight the various neuromodulation systems, their general perioperative considerations, and notable special circumstances for perioperative management.
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Affiliation(s)
- Vwaire Orhurhu
- Anesthesiology, University of Pittsburgh Medical Center, Williamsport, Pennsylvania, USA
- Pain Medicine, MVM Health, East Stroudsburg, Pennsylvania, USA
| | - Nasir Hussain
- Department of Anesthesiology, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Jay Karri
- Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, Texas, USA
| | - Edward R Mariano
- Anesthesiology and Perioperative Care Service, VA Palo Alto Health Care System, Palo Alto, California, USA
- Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California, USA
| | - Alaa Abd-Elsayed
- Department of Anesthesia, Divsion of Pain Medicine, University of Wisconsin Madison School of Medicine and Public Health, Madison, Wisconsin, USA
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Klingbeil J, Brandt ML, Stockert A, Baum P, Hoffmann KT, Saur D, Wawrzyniak M. Associations of lesion location, structural disconnection, and functional diaschisis with depressive symptoms post stroke. Front Neurol 2023; 14:1144228. [PMID: 37265471 PMCID: PMC10231644 DOI: 10.3389/fneur.2023.1144228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Accepted: 04/20/2023] [Indexed: 06/03/2023] Open
Abstract
Introduction Post-stroke depressive symptoms (PSDS) are common and relevant for patient outcome, but their complex pathophysiology is ill understood. It likely involves social, psychological and biological factors. Lesion location is a readily available information in stroke patients, but it is unclear if the neurobiological substrates of PSDS are spatially localized. Building on previous analyses, we sought to determine if PSDS are associated with specific lesion locations, structural disconnection and/or localized functional diaschisis. Methods In a prospective observational study, we examined 270 patients with first-ever stroke with the Hospital Anxiety and Depression Scale (HADS) around 6 months post-stroke. Based on individual lesion locations and the depression subscale of the HADS we performed support vector regression lesion-symptom mapping, structural-disconnection-symptom mapping and functional lesion network-symptom-mapping, in a reanalysis of this previously published cohort to infer structure-function relationships. Results We found that depressive symptoms were associated with (i) lesions in the right insula, right putamen, inferior frontal gyrus and right amygdala and (ii) structural disconnection in the right temporal lobe. In contrast, we found no association with localized functional diaschisis. In addition, we were unable to confirm a previously described association between depressive symptom load and a network damage score derived from functional disconnection maps. Discussion Based on our results, and other recent lesion studies, we see growing evidence for a prominent role of right frontostriatal brain circuits in PSDS.
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Affiliation(s)
- Julian Klingbeil
- Neuroimaging Laboratory, Department of Neurology, University of Leipzig Medical Center, Leipzig, Germany
| | - Max-Lennart Brandt
- Neuroimaging Laboratory, Department of Neurology, University of Leipzig Medical Center, Leipzig, Germany
| | - Anika Stockert
- Neuroimaging Laboratory, Department of Neurology, University of Leipzig Medical Center, Leipzig, Germany
| | - Petra Baum
- Department of Neurology, University of Leipzig Medical Center, Leipzig, Germany
| | - Karl-Titus Hoffmann
- Department of Neuroradiology, University of Leipzig Medical Center, Leipzig, Germany
| | - Dorothee Saur
- Neuroimaging Laboratory, Department of Neurology, University of Leipzig Medical Center, Leipzig, Germany
| | - Max Wawrzyniak
- Neuroimaging Laboratory, Department of Neurology, University of Leipzig Medical Center, Leipzig, Germany
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Omlor N, Richter M, Goltermann J, Steinmann LA, Kraus A, Borgers T, Klug M, Enneking V, Redlich R, Dohm K, Repple J, Leehr EJ, Grotegerd D, Kugel H, Bauer J, Dannlowski U, Opel N. Treatment with the second-generation antipsychotic quetiapine is associated with increased subgenual ACC activation during reward processing in major depressive disorder. J Affect Disord 2023; 329:404-412. [PMID: 36842646 DOI: 10.1016/j.jad.2023.02.102] [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: 09/08/2022] [Revised: 02/10/2023] [Accepted: 02/20/2023] [Indexed: 02/28/2023]
Abstract
BACKGROUND The second-generation antipsychotic (SGA) quetiapine is an essential option for antidepressant augmentation therapy in major depressive disorder (MDD), yet neurobiological mechanisms behind its antidepressant properties remain unclear. As SGAs interfere with activity in reward-related brain areas, including the anterior cingulate cortex (ACC) - a key brain region in antidepressant interventions, this study examined whether quetiapine treatment affects ACC activity during reward processing in MDD patients. METHODS Using the ACC as region of interest, an independent t-test comparing reward-related BOLD response of 51 quetiapine-taking and 51 antipsychotic-free MDD patients was conducted. Monetary reward outcome feedback was measured in a card-guessing paradigm using pseudorandom blocks. Participants were matched for age, sex, and depression severity and analyses were controlled for confounding variables, including total antidepressant medication load, illness chronicity and acute depression severity. Potential dosage effects were examined in a 3 × 1 ANOVA. Differences in ACC-related functional connectivity were assessed in psycho-physiological interaction (PPI) analyses. RESULTS Left subgenual ACC activity was significantly higher in the quetiapine group compared to antipsychotic-free participants and dependent on high-dose quetiapine intake. Results remained significant after controlling for confounding variables. The PPI analysis did not yield significant group differences in ACC-related functional connectivity. LIMITATIONS Causal interpretation is limited due to cross-sectional findings. CONCLUSION Elevated subgenual ACC activity to rewarding stimuli may represent a neurobiological marker and potential key interface of quetiapine's antidepressant effects in MDD. These results underline ACC activity during reward processing as an investigative avenue for future research and therapeutic interventions to improve MDD treatment outcomes.
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Affiliation(s)
- Nicola Omlor
- Institute for Translational Psychiatry, University of Münster, Germany
| | - Maike Richter
- Institute for Translational Psychiatry, University of Münster, Germany; Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany
| | - Janik Goltermann
- Institute for Translational Psychiatry, University of Münster, Germany
| | | | - Anna Kraus
- Institute for Translational Psychiatry, University of Münster, Germany
| | - Tiana Borgers
- Institute for Translational Psychiatry, University of Münster, Germany
| | - Melissa Klug
- Institute for Translational Psychiatry, University of Münster, Germany
| | - Verena Enneking
- Institute for Translational Psychiatry, University of Münster, Germany
| | - Ronny Redlich
- Institute for Translational Psychiatry, University of Münster, Germany; Department of Psychology, Martin-Luther University of Halle, Germany; German Center for Mental Health (DZPG), Site Jena-Magdeburg-Halle, Germany
| | - Katharina Dohm
- Institute for Translational Psychiatry, University of Münster, Germany
| | - Jonathan Repple
- Institute for Translational Psychiatry, University of Münster, Germany
| | - Elisabeth J Leehr
- Institute for Translational Psychiatry, University of Münster, Germany
| | - Dominik Grotegerd
- Institute for Translational Psychiatry, University of Münster, Germany
| | - Harald Kugel
- University Clinic for Radiology, University of Münster, Germany
| | - Jochen Bauer
- University Clinic for Radiology, University of Münster, Germany
| | - Udo Dannlowski
- Institute for Translational Psychiatry, University of Münster, Germany
| | - Nils Opel
- Institute for Translational Psychiatry, University of Münster, Germany; Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany; Center for Intervention and Research on adaptive and maladaptive brain Circuits underlying mental health (C-I-R-C), Jena-Magdeburg-Halle, Germany; German Center for Mental Health (DZPG), Site Jena-Magdeburg-Halle, Germany.
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Falkowska M, Ntamati NR, Nevian NE, Nevian T, Acuña MA. Environmental enrichment promotes resilience to neuropathic pain-induced depression and correlates with decreased excitability of the anterior cingulate cortex. Front Behav Neurosci 2023; 17:1139205. [PMID: 37008999 PMCID: PMC10060563 DOI: 10.3389/fnbeh.2023.1139205] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Accepted: 02/27/2023] [Indexed: 03/18/2023] Open
Abstract
Depression is a common comorbidity of chronic pain with many patients being affected. However, efficient pharmacological treatment strategies are still lacking. Therefore, it is desirable to find additional alternative approaches. Environmental enrichment has been suggested as a method to alleviate pain-induced depression. However, the neuronal mechanisms of its beneficial effects are still elusive. The anterior cingulate cortex (ACC) plays a central role in processing pain-related negative affect and chronic pain-induced plasticity in this region correlates with depressive symptoms. We studied the consequences of different durations of environmental enrichment on pain sensitivity and chronic pain-induced depression-like behaviors in a mouse model of neuropathic pain. Furthermore, we correlated the behavioral outcomes to the activity levels of pyramidal neurons in the ACC by analyzing their electrophysiological properties ex vivo. We found that early exposure to an enriched environment alone was not sufficient to cause resilience against pain-induced depression-like symptoms. However, extending the enrichment after the injury prevented the development of depression and reduced mechanical hypersensitivity. On the cellular level, increased neuronal excitability was associated with the depressive phenotype that was reversed by the enrichment. Therefore, neuronal excitability in the ACC was inversely correlated to the extended enrichment-induced resilience to depression. These results suggest that the improvement of environmental factors enhanced the resilience to developing chronic pain-related depression. Additionally, we confirmed the association between increased neuronal excitability in the ACC and depression-like states. Therefore, this non-pharmacological intervention could serve as a potential treatment strategy for comorbid symptoms of chronic pain.
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Zhang Y, Ma L, Zhang X, Yue L, Wang J, Zheng J, Cui S, Liu FY, Wang Z, Wan Y, Yi M. Deep brain stimulation in the lateral habenula reverses local neuronal hyperactivity and ameliorates depression-like behaviors in rats. Neurobiol Dis 2023; 180:106069. [PMID: 36893902 DOI: 10.1016/j.nbd.2023.106069] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2023] [Revised: 02/22/2023] [Accepted: 03/04/2023] [Indexed: 03/09/2023] Open
Abstract
Deep brain stimulation (DBS) is a promising therapy for treatment-resistant depression, while mechanisms underlying its therapeutic effects remain poorly defined. Increasing evidence has revealed an intimate association between the lateral habenula (LHb) and major depression, and suggests that the LHb might be an effective target of DBS therapy for depression. Here, we found that DBS in the LHb effectively decreased depression-like behaviors in rats experienced with chronic unpredictable mild stress (CUMS), a well-accepted paradigm for modeling depression in rodents. In vivo electrophysiological recording unveiled that CUMS increased neuronal burst firing, as well as the proportion of neurons showing hyperactivity to aversive stimuli in the LHb. Nevertheless, DBS downregulated local field potential power, reversed the CUMS-induced increase of LHb burst firing and neuronal hyperactivity to aversive stimuli, and decreased the coherence between LHb and ventral tegmental area (VTA). Our results demonstrate that DBS in the LHb exerts antidepressant-like effects and reverses local neural hyperactivity, supporting the LHb as a target of DBS therapy for depression.
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Affiliation(s)
- Yuqi Zhang
- Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, PR China
| | - Longyu Ma
- Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, PR China
| | - Xueying Zhang
- Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
| | - Lupeng Yue
- CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Science, Beijing 100101, China
| | - Jiaxin Wang
- Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, PR China
| | - Jie Zheng
- Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, PR China
| | - Shuang Cui
- Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, PR China
| | - Feng-Yu Liu
- Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, PR China
| | - Zhiyan Wang
- CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Science, Beijing 100101, China; National Engineering Laboratory for Neuromodulation, School of Aerospace Engineering, Tsinghua University, Beijing 100084, China.
| | - You Wan
- Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, PR China; Key Laboratory for Neuroscience, Ministry of Education/National Health Commission, Peking University, Beijing 100083, PR China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
| | - Ming Yi
- Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, PR China; Key Laboratory for Neuroscience, Ministry of Education/National Health Commission, Peking University, Beijing 100083, PR China.
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Jiang Y, Zou M, Wang Y, Wang Y. Nucleus accumbens in the pathogenesis of major depressive disorder: A brief review. Brain Res Bull 2023; 196:68-75. [PMID: 36889362 DOI: 10.1016/j.brainresbull.2023.03.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 02/16/2023] [Accepted: 03/05/2023] [Indexed: 03/08/2023]
Abstract
Major depressive disorder (MDD) is the most prevalent mental disorder characterized by anhedonia, loss of motivation, avolition, behavioral despair and cognitive abnormalities. Despite substantial advancements in the pathophysiology of MDD in recent years, the pathogenesis of this disorder is not fully understood. Meanwhile,the treatment of MDD with currently available antidepressants is inadequate, highlighting the urgent need for clarifying the pathophysiology of MDD and developing novel therapeutics. Extensive studies have demonstrated the involvement of nuclei such as the prefrontal cortex (PFC), hippocampus (HIP), nucleus accumbens (NAc), hypothalamus, etc., in MDD. NAc,a region critical for reward and motivation,dysregulation of its activity seems to be a hallmark of this mood disorder. In this paper, we present a review of NAc related circuits, cellular and molecular mechanisms underlying MDD and share an analysis of the gaps in current research and possible future research directions.
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Affiliation(s)
- Yajie Jiang
- Institute of Innovation and Applied Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China; Hunan Key Laboratory of Traditional Chinese Medicine Prevention & Treatment of Depressive Diseases, Changsha, China
| | - Manshu Zou
- Hunan Key Laboratory of Traditional Chinese Medicine Prevention & Treatment of Depressive Diseases, Changsha, China
| | - Yeqing Wang
- State Key Laboratory of Developmental Biology of Freshwater Fish, Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Laboratory of Animal Nutrition and Human Health, College of Life Sciences, Hunan Normal University, Changsha 410081, China
| | - Yuhong Wang
- Institute of Innovation and Applied Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China; Hunan Key Laboratory of Traditional Chinese Medicine Prevention & Treatment of Depressive Diseases, Changsha, China.
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Lo C, Mane M, Kim JH, Berk M, Sharp RR, Lee KH, Yuen J. Treating addiction with deep brain stimulation: Ethical and legal considerations. THE INTERNATIONAL JOURNAL OF DRUG POLICY 2023; 113:103964. [PMID: 36774790 PMCID: PMC10023340 DOI: 10.1016/j.drugpo.2023.103964] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 01/27/2023] [Accepted: 01/28/2023] [Indexed: 02/12/2023]
Abstract
BACKGROUND The use of neuromodulation in the treatment of psychiatric conditions is controversial despite its lengthy history. This particularly applies to the use of invasive neuromodulation, such as deep brain stimulation (DBS), to treat substance use disorder (SUD) due to the considerable risks of the procedures. However, given the advances in DBS research and the shortcomings of current treatment modalities for addiction, off-label use and clinical trials are being implemented for the management of treatment-refractory patients. METHODS Here we conduct an ethical and legal analysis of DBS for SUD, referencing the four foundational principles of medical ethics and key legal concepts. RESULTS There are major concerns related to the capacity of a SUD patient to provide informed consent, as well as the risks and benefits of DBS compared to traditional treatment methods. In addition to ethical concerns, we explore potential legal issues that may arise from DBS in the treatment of addiction. These include the potential mandate of these procedures in the context of the criminalization of substance use, and the issue of familial consent in the decision-making process. Given the paucity of relevant clinical guidelines or legal cases, general medico-legal principles serve as the reference in making decisions about the responsible use of DBS as a treatment for addiction. CONCLUSIONS Given the rapidly increasing evidence for DBS as a treatment for SUD, it is an urgent imperative to consider the relevant key ethical and legal issues. Incorporating IDEAL (Idea, Development, Exploration, Assessment, Long-term follow-up) framework into future research in DBS is recommended to evaluate patient safety and ethical perspectives. With the broad criminalization of SUD across the globe, legal coercion of DBS is not impossible, especially if proven to be effective to treat SUD. It is advised for stakeholders to urgently consider incorporating DBS-related drug policies so that the potential benefits of DBS within the rights of people with SUD are not hindered by the lack of clinical guidance and legislations.
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Affiliation(s)
- Clara Lo
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA; Macalester College, St. Paul, MN 55105, USA
| | - Mansee Mane
- University of Minnesota, Minneapolis, MN 55455, USA
| | - Jee Hyun Kim
- Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong VIC 3216, Australia
| | - Michael Berk
- Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong VIC 3216, Australia
| | - Richard R Sharp
- Biomedical Ethics Program, Mayo Clinic, Rochester, MN 55905, USA
| | - Kendall H Lee
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA; Department of Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA
| | - Jason Yuen
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA; Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong VIC 3216, Australia.
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D’Onofrio V, Manzo N, Guerra A, Landi A, Baro V, Määttä S, Weis L, Porcaro C, Corbetta M, Antonini A, Ferreri F. Combining Transcranial Magnetic Stimulation and Deep Brain Stimulation: Current Knowledge, Relevance and Future Perspectives. Brain Sci 2023; 13:brainsci13020349. [PMID: 36831892 PMCID: PMC9954740 DOI: 10.3390/brainsci13020349] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 02/13/2023] [Accepted: 02/16/2023] [Indexed: 02/22/2023] Open
Abstract
Deep brain stimulation (DBS) has emerged as an invasive neuromodulation technique for the treatment of several neurological disorders, but the mechanisms underlying its effects remain partially elusive. In this context, the application of Transcranial Magnetic Stimulation (TMS) in patients treated with DBS represents an intriguing approach to investigate the neurophysiology of cortico-basal networks. Experimental studies combining TMS and DBS that have been performed so far have mainly aimed to evaluate the effects of DBS on the cerebral cortex and thus to provide insights into DBS's mechanisms of action. The modulation of cortical excitability and plasticity by DBS is emerging as a potential contributor to its therapeutic effects. Moreover, pairing DBS and TMS stimuli could represent a method to induce cortical synaptic plasticity, the therapeutic potential of which is still unexplored. Furthermore, the advent of new DBS technologies and novel treatment targets will present new research opportunities and prospects to investigate brain networks. However, the application of the combined TMS-DBS approach is currently limited by safety concerns. In this review, we sought to present an overview of studies performed by combining TMS and DBS in neurological disorders, as well as available evidence and recommendations on the safety of their combination. Additionally, we outline perspectives for future research by highlighting knowledge gaps and possible novel applications of this approach.
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Affiliation(s)
| | - Nicoletta Manzo
- IRCCS San Camillo Hospital, Via Alberoni 70, 0126 Venice, Italy
| | - Andrea Guerra
- IRCCS Neuromed, 86077 Pozzilli, Italy
- Department of Human Neurosciences, Sapienza University of Rome, 00185 Rome, Italy
| | - Andrea Landi
- Academic Neurosurgery, Department of Neurosciences, University of Padova, 35128 Padova, Italy
| | - Valentina Baro
- Academic Neurosurgery, Department of Neurosciences, University of Padova, 35128 Padova, Italy
| | - Sara Määttä
- Department of Clinical Neurophysiology, Kuopio University Hospital, University of Eastern Finland, 70211 Kuopio, Finland
| | - Luca Weis
- Parkinson’s Disease and Movement Disorders Unit, Department of Neuroscience, Centre for Rare Neurological Diseases (ERN-RND), University of Padova, 35128 Padova, Italy
| | - Camillo Porcaro
- Padova Neuroscience Center (PNC), University of Padova, 35129 Padova, Italy
- Department of Neuroscience, University of Padova, 35128 Padova, Italy
- Institute of Cognitive Sciences, and Technologies (ISTC)-National Research Council (CNR), 00185 Rome, Italy
- Centre for Human Brain Health, School of Psychology, University of Birmingham, Birmingham B15 2TT, UK
| | - Maurizio Corbetta
- Padova Neuroscience Center (PNC), University of Padova, 35129 Padova, Italy
- Unit of Neurology, Unit of Clinical Neurophysiology, Study Center of Neurodegeneration (CESNE), Department of Neuroscience, University of Padova, 35128 Padova, Italy
- Venetian Institute of Molecular Medicine, 35129 Padova, Italy
| | - Angelo Antonini
- Parkinson’s Disease and Movement Disorders Unit, Department of Neuroscience, Centre for Rare Neurological Diseases (ERN-RND), University of Padova, 35128 Padova, Italy
- Unit of Neurology, Unit of Clinical Neurophysiology, Study Center of Neurodegeneration (CESNE), Department of Neuroscience, University of Padova, 35128 Padova, Italy
- Department of Neurology, Washington University, St. Louis, MO 63108, USA
- Department of Neuroscience, Washington University, St. Louis, MO 63108, USA
- Correspondence: (A.A.); (F.F.)
| | - Florinda Ferreri
- Department of Clinical Neurophysiology, Kuopio University Hospital, University of Eastern Finland, 70211 Kuopio, Finland
- Unit of Neurology, Unit of Clinical Neurophysiology, Study Center of Neurodegeneration (CESNE), Department of Neuroscience, University of Padova, 35128 Padova, Italy
- Correspondence: (A.A.); (F.F.)
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Tik M, Woletz M, Schuler AL, Vasileiadi M, Cash RFH, Zalesky A, Lamm C, Windischberger C. Acute TMS/fMRI response explains offline TMS network effects - An interleaved TMS-fMRI study. Neuroimage 2023; 267:119833. [PMID: 36572133 DOI: 10.1016/j.neuroimage.2022.119833] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 11/22/2022] [Accepted: 12/22/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Transcranial magnetic stimulation (TMS) is an FDA-approved therapeutic option for treatment resistant depression. However, exact mechanisms-of-action are not fully understood and individual responses are variable. Moreover, although previously suggested, the exact network effects underlying TMS' efficacy are poorly understood as of today. Although, it is supposed that DLPFC stimulation indirectly modulates the sgACC, recent evidence is sparse. METHODS Here, we used concurrent interleaved TMS/fMRI and state-of-the-science purpose-designed MRI head coils to delineate networks and downstream regions activated by DLPFC-TMS. RESULTS We show that regions of increased acute BOLD signal activation during TMS resemble a resting-state brain network previously shown to be modulated by offline TMS. There was a topographical overlap in wide spread cortical and sub-cortical areas within this specific RSN#17 derived from the 1000 functional connectomes project. CONCLUSION These data imply a causal relation between DLPFC-TMS and activation of the ACC and a broader network that has been implicated in MDD. In the broader context of our recent work, these data imply a direct relation between initial changes in BOLD activity mediated by connectivity to the DLPFC target site, and later consolidation of connectivity between these regions. These insights advance our understanding of the mechanistic targets of DLPFC-TMS and may provide novel opportunities to characterize and optimize TMS therapy in other neurological and psychiatric disorders.
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Affiliation(s)
- M Tik
- High-Field MR Center, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Austria
| | - M Woletz
- High-Field MR Center, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Austria
| | - A-L Schuler
- High-Field MR Center, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Austria
| | - M Vasileiadi
- High-Field MR Center, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Austria
| | - R F H Cash
- Melbourne Neuropsychiatry Centre, University of Melbourne, Melbourne, Victoria, Australia; Department of Biomedical Engineering, University of Melbourne, Melbourne, Victoria, Australia
| | - A Zalesky
- Melbourne Neuropsychiatry Centre, University of Melbourne, Melbourne, Victoria, Australia; Department of Biomedical Engineering, University of Melbourne, Melbourne, Victoria, Australia
| | - C Lamm
- Social Cognitive and Affective Neuroscience Unit, Department of Cognition, Emotion, and Methods in Psychology, Faculty of Psychology, University of Vienna, Austria
| | - C Windischberger
- High-Field MR Center, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Austria.
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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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Ausderau KK, Colman RJ, Kabakov S, Schultz-Darken N, Emborg ME. Evaluating depression- and anxiety-like behaviors in non-human primates. Front Behav Neurosci 2023; 16:1006065. [PMID: 36744101 PMCID: PMC9892652 DOI: 10.3389/fnbeh.2022.1006065] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 12/29/2022] [Indexed: 01/20/2023] Open
Abstract
Depression and anxiety are some of the most prevalent and debilitating mental health conditions in humans. They can present on their own or as co-morbidities with other disorders. Like humans, non-human primates (NHPs) can develop depression- and anxiety-like signs. Here, we first define human depression and anxiety, examine equivalent species-specific behaviors in NHPs, and consider models and current methods to identify and evaluate these behaviors. We also discuss knowledge gaps, as well as the importance of evaluating the co-occurrence of depression- and anxiety-like behaviors in animal models of human disease. Lastly, we consider ethical challenges in depression and anxiety research on NHPs in order to ultimately advance the understanding and the personalized treatment of these disorders.
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Affiliation(s)
- Karla K. Ausderau
- Wisconsin National Primate Research Center, University of Wisconsin—Madison, Madison, WI, United States
- Waisman Center, University of Wisconsin—Madison, Madison, WI, United States
- Department of Kinesiology, University of Wisconsin—Madison, Madison, WI, United States
| | - Ricki J. Colman
- Wisconsin National Primate Research Center, University of Wisconsin—Madison, Madison, WI, United States
- Department of Cell and Regenerative Biology, University of Wisconsin—Madison, Madison, WI, United States
| | - Sabrina Kabakov
- Department of Kinesiology, University of Wisconsin—Madison, Madison, WI, United States
| | - Nancy Schultz-Darken
- Wisconsin National Primate Research Center, University of Wisconsin—Madison, Madison, WI, United States
| | - Marina E. Emborg
- Wisconsin National Primate Research Center, University of Wisconsin—Madison, Madison, WI, United States
- Department of Medical Physics, University of Wisconsin—Madison, Madison, WI, United States
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Hung CI, Wu CT, Chao YP. Differences in gray matter volumes of subcortical nuclei between major depressive disorder with and without persistent depressive disorder. J Affect Disord 2023; 321:161-166. [PMID: 36272460 DOI: 10.1016/j.jad.2022.10.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Revised: 10/01/2022] [Accepted: 10/17/2022] [Indexed: 11/17/2022]
Abstract
OBJECTIVE This study aimed to compare the differences in gray matter volumes (GMVs) of subcortical nuclei between major depressive disorder (MDD) patients with and without persistent depressive disorder (PDD) at long-term follow-up. METHODS 114 and 94 subjects with MDD, including 48 and 41 with comorbid PDD, were enrolled to undergo high-resolution T1-weighted imaging at first (FIP) and second (three years later, SIP) investigation points, respectively. FreeSurfer was used to extract the GMVs of seven subcortical nuclei, and Generalized Estimating Equation models were employed to estimate the differences in GMVs of subcortical nuclei between the two subgroups. RESULTS The PDD subgroup had a significantly greater depressive severity and a higher percentage of patients undergoing pharmacotherapy at the FIP as compared with the non-PDD subgroup. These differences became insignificant at the SIP. The PDD subgroup had a significantly (p < 0.003) smaller GMV in the right putamen at the SIP and in the right nucleus accumbens (NAc) at the FIP and SIP as compared with the non-PDD subgroup. After controlling for clinical variables, PDD was independently associated with smaller GMVs in the right putamen and NAc. LIMITATIONS Imaging was not performed at baseline and pharmacotherapy was not controlled at the FIP and SIP. CONCLUSIONS MDD with PDD was associated with smaller GMVs in the right putamen and NAc as compared with MDD without PDD. Whether the two regions are biomarkers related to a poor prognosis and the chronicity of depression requires further study.
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Affiliation(s)
- Ching-I Hung
- Department of Psychiatry, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chen-Te Wu
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Yi-Ping Chao
- Graduate Institute of Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan; Department of Computer Science and Information Engineering, Chang Gung University, Taoyuan, Taiwan; Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
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Kustubayeva A, Eliassen J, Matthews G, Nelson E. FMRI study of implicit emotional face processing in patients with MDD with melancholic subtype. Front Hum Neurosci 2023; 17:1029789. [PMID: 36923587 PMCID: PMC10009191 DOI: 10.3389/fnhum.2023.1029789] [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: 08/27/2022] [Accepted: 01/30/2023] [Indexed: 03/02/2023] Open
Abstract
Introduction The accurate perception of facial expressions plays a vital role in daily life, allowing us to select appropriate responses in social situations. Understanding the neuronal basis of altered emotional face processing in patients with major depressive disorder (MDD) may lead to the appropriate choice of individual interventions to help patients maintain social functioning during depressive episodes. Inconsistencies in neuroimaging studies of emotional face processing are caused by heterogeneity in neurovegetative symptoms of depressive subtypes. The aim of this study was to investigate brain activation differences during implicit perception of faces with negative and positive emotions between healthy participants and patients with melancholic subtype of MDD. The neurobiological correlates of sex differences of MDD patients were also examined. Methods Thirty patients diagnosed with MDD and 21 healthy volunteers were studied using fMRI while performing an emotional face perception task. Results Comparing general face activation irrespective of emotional content, the intensity of BOLD signal was significantly decreased in the left thalamus, right supramarginal gyrus, right and left superior frontal gyrus, right middle frontal gyrus, and left fusiform gyrus in patients with melancholic depression compared to healthy participants. We observed only limited mood-congruence in response to faces of differing emotional valence. Brain activation in the middle temporal gyrus was significantly increased in response to fearful faces in comparison to happy faces in MDD patients. Elevated activation was observed in the right cingulate for happy and fearful faces, in precuneus for happy faces, and left posterior cingulate cortex for all faces in depressed women compared to men. The Inventory for Depressive Symptomatology (IDS) score was inversely correlated with activation in the left subgenual gyrus/left rectal gyrus for sad, neutral, and fearful faces in women in the MDD group. Patients with melancholic features performed similarly to controls during implicit emotional processing but showed reduced activation. Discussion and conclusion This finding suggests that melancholic patients compensate for reduced brain activation when interpreting emotional content in order to perform similarly to controls. Overall, frontal hypoactivation in response to implicit emotional stimuli appeared to be the most robust feature of melancholic depression.
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Affiliation(s)
- Almira Kustubayeva
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, College of Medicine, Cincinnati, OH, United States.,Center for Cognitive Neuroscience, Department of Biophysics, Biomedicine, and Neuroscience, Al-Farabi Kazakh National University, Almaty, Kazakhstan.,National Centre for Neurosurgery, Astana, Kazakhstan
| | - James Eliassen
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, College of Medicine, Cincinnati, OH, United States.,Robert Bosch Automotive Steering, Florence, KY, United States
| | - Gerald Matthews
- Department of Psychology, George Mason University, Fairfax, VA, United States
| | - Erik Nelson
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, College of Medicine, Cincinnati, OH, United States
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Prolonged Longitudinal Transcutaneous Auricular Vagus Nerve Stimulation Effect on Striatal Functional Connectivity in Patients with Major Depressive Disorder. Brain Sci 2022; 12:brainsci12121730. [PMID: 36552189 PMCID: PMC9776392 DOI: 10.3390/brainsci12121730] [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: 10/21/2022] [Revised: 12/11/2022] [Accepted: 12/15/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Transcutaneous auricular vagus nerve stimulation (taVNS) is effective for treating major depressive disorder (MDD). We aimed to explore the modulating effect of prolonged longitudinal taVNS on the striatal subregions' functional connectivity (FC) in MDD patients. METHODS Sixteen MDD patients were enrolled and treated with taVNS for 8 weeks. Sixteen healthy control subjects (HCs) were recruited without intervention. The resting-state FC (rsFC) based on striatal subregion seed points and the Hamilton Depression Scale (HAMD) were evaluated in the MDD patients and HCs at baseline and after 8 weeks. A two-way ANCOVA test was performed on each rsFC metric to obtain the (group-by-time) interactions. RESULTS The rsFC values between the left ventral caudate (vCa) and right ventral prefrontal cortex (vPFC), and between the right nucleus accumbens (NAc) and right dorsal medial prefrontal cortex (dmPFC) and ventrolateral prefrontal cortex (vlPFC) are lower in the MDD patients compared to the HCs at baseline, and increase following taVNS; the rsFC values between the left vCa and right, superior occipital gyrus (SOG), and between the left dorsal caudate (dCa) and right cuneus are higher in MDD patients and decrease following taVNS. CONCLUSIONS Prolonged longitudinal taVNS can modulate the striatum rsFC with the prefrontal cortex, occipital cortex, temporal cortex, and intra-striatum, and these changes partly underlie any symptomatic improvements. The results indicate that prolonged longitudinal taVNS may produce beneficial treatment effects by modulating the cortical striatum circuitry in patients with MDD.
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White Matter Microstructure Associated with the Antidepressant Effects of Deep Brain Stimulation in Treatment-Resistant Depression: A Review of Diffusion Tensor Imaging Studies. Int J Mol Sci 2022; 23:ijms232315379. [PMID: 36499706 PMCID: PMC9738114 DOI: 10.3390/ijms232315379] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 11/23/2022] [Accepted: 12/01/2022] [Indexed: 12/13/2022] Open
Abstract
Treatment-resistant depression (TRD) is a severe disorder characterized by high relapse rates and decreased quality of life. An effective strategy in the management of TRD is deep brain stimulation (DBS), a technique consisting of the implantation of electrodes that receive a stimulation via a pacemaker-like stimulator into specific brain areas, detected through neuroimaging investigations, which include the subgenual cingulate cortex (sgCC), basal ganglia, and forebrain bundles. In this context, to improve our understanding of the mechanism underlying the antidepressant effects of DBS in TRD, we collected the results of diffusion tensor imaging (DTI) studies exploring how WM microstructure is associated with the therapeutic effects of DBS in TRD. A search on PubMed, Web of Science, and Scopus identified 11 investigations assessing WM microstructure in responders and non-responders to DBS. Altered WM microstructure, particularly in the sgCC, medial forebrain bundle, cingulum bundle, forceps minor, and uncinate fasciculus, was associated with the antidepressant effect of DBS in TRD. Overall, the results show that DBS targeting selective brain regions, including the sgCC, forebrain bundle, cingulum bundle, rectus gyrus, anterior limb of the internal capsule, forceps minor, and uncinate fasciculus, seem to be effective for the treatment of TRD.
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Pope E, Muthukrishnan S, Phillips J, Phillips S. A case of treatment-resistant depression in an older adult and a discussion of treatment options. BJPsych Bull 2022; 46:331-336. [PMID: 34782028 PMCID: PMC9813956 DOI: 10.1192/bjb.2021.105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Treatment-resistant depression is a complex condition often requiring specialist psychiatric care. Many different psychiatric, physical and social factors can lead to a poor response to initial treatment of depression, and a careful assessment is required to determine the most appropriate management option. This can be particularly complex in the older population, who often have multiple physical and social comorbidities. We have used a fictional case to illustrate this, alongside an anonymised vignette of someone with personal experience of this condition. We have also provided an overview of the current evidence for treatment options, as well as a discussion of potential aetiological factors. By the end of this article, readers should understand the ambiguity of this diagnostic term, the aetiological factors that need to be assessed and the rationale for the treatment options available. They should be able to recognise how these ideas apply to the geriatric population.
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Affiliation(s)
| | - Sabari Muthukrishnan
- Avon and Wiltshire Mental Health Partnership NHS Trust, UK.,Kingshill Research Centre, UK
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