|
1
|
Chen SH, Lan B, Zhang YY, Li GH, Qian YL, Hu MX, Tian YL, Zang WD, Cao J, Wang GH, Wang YG. Activation of zona incerta gamma-aminobutyric acid-ergic neurons alleviates depression-like and anxiety-like behaviors induced by chronic restraint stress. World J Psychiatry 2025; 15:101807. [PMID: 39974487 PMCID: PMC11758062 DOI: 10.5498/wjp.v15.i2.101807] [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] [Received: 09/27/2024] [Revised: 11/25/2024] [Accepted: 12/18/2024] [Indexed: 01/14/2025] Open
Abstract
BACKGROUND Depression is a prevalent affective disorder, but its pathophysiology remains unclear. Dysfunction in the gamma-aminobutyric acid (GABA)-ergic system may contribute to its onset. Recently, antidepressants (e.g., brexanolone, zuranolone) targeting the GABA-A receptor were introduced. The zona incerta (ZI), an inhibitory subthalamic region mainly composed of GABAergic neurons, has been implicated in emotional regulation. Deep brain stimulation of the ZI in humans affects anxiety and depression symptoms, while activation of ZI neurons in mice can either worsen or alleviate anxiety. Currently, there is no direct evidence linking GABAergic neurons in the ZI to depression-like behaviors in rodents. AIM To explore the relationship between GABAergic neurons in the ZI and depression-like behaviors in mice. METHODS A chronic restraint stress (CRS) model was utilized to induce depression in mice. Whole-cell patch-clamp recordings assessed the excitability changes of GABAergic neurons in the ZI. Additionally, chemogenetic techniques were employed to modulate ZI GABAergic neurons. The performance of the mice in behavioral tests for depression and anxiety was observed. RESULTS The findings indicated that GABAergic neurons in the ZI were closely associated with depression-like behaviors in mice. Twenty-eight days after the CRS model was established, depression-like and anxiety-like behaviors were observed in the mice. The excitability of GABAergic neurons in the ZI was reduced. Chemogenetic activation of these neurons alleviated CRS-induced depression-like and anxiety-like behaviors. Conversely, inhibition of GABAergic neurons in the ZI led to changes in emotion-related behavioral outcomes in mice. CONCLUSION Activity of GABAergic neurons in the ZI was closely associated with depression-like phenotypes in mice, suggesting that these neurons could be a potential therapeutic target for treating depression.
Collapse
Affiliation(s)
- Si-Hai Chen
- Department of Psychiatry, Xiaogan Rehabilitation Hospital, Xiaogan 432000, Hubei Province, China
- School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, Henan Province, China
| | - Bo Lan
- Department of Psychiatry, Xiaogan Rehabilitation Hospital, Xiaogan 432000, Hubei Province, China
| | - Ying-Ying Zhang
- School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, Henan Province, China
| | - Guo-Hui Li
- Department of Psychiatry, Xiaogan Rehabilitation Hospital, Xiaogan 432000, Hubei Province, China
| | - Yu-Long Qian
- Department of Psychiatry, Xiaogan Rehabilitation Hospital, Xiaogan 432000, Hubei Province, China
| | - Ming-Xing Hu
- Department of Psychiatry, Xiaogan Rehabilitation Hospital, Xiaogan 432000, Hubei Province, China
| | - Yin-Lin Tian
- Department of Psychiatry, Xiaogan Rehabilitation Hospital, Xiaogan 432000, Hubei Province, China
| | - Wei-Dong Zang
- School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, Henan Province, China
| | - Jing Cao
- School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, Henan Province, China
- School of Nursing and Health, Zhengzhou University, Zhengzhou 450000, Henan Province, China
| | - Guang-Hai Wang
- Department of Psychiatry, Xiaogan Rehabilitation Hospital, Xiaogan 432000, Hubei Province, China
| | - Yi-Gang Wang
- Department of Psychiatry, Xiaogan Rehabilitation Hospital, Xiaogan 432000, Hubei Province, China
| |
Collapse
|
|
2
|
Wilt M, Magnard R, Carnicella S, Vachez YM. Zona incerta: from Parkinson's disease to addiction. Front Neural Circuits 2025; 19:1537449. [PMID: 39991498 PMCID: PMC11839659 DOI: 10.3389/fncir.2025.1537449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Accepted: 01/27/2025] [Indexed: 02/25/2025] Open
Affiliation(s)
- Mylène Wilt
- Inserm, U1216, Univ. Grenoble Alpes, Grenoble Institut Neurosciences, Grenoble, France
| | - Robin Magnard
- Department of Psychological and Brain Sciences, Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD, United States
| | - Sebastien Carnicella
- Inserm, U1216, Univ. Grenoble Alpes, Grenoble Institut Neurosciences, Grenoble, France
| | - Yvan M. Vachez
- Inserm, U1216, Univ. Grenoble Alpes, Grenoble Institut Neurosciences, Grenoble, France
| |
Collapse
|
|
3
|
Scerrati A, Gozzi A, Cavallo MA, Mantovani G, Antenucci P, Angelini C, Capone JG, De Bonis P, Morgante F, Rispoli V, Sensi M. Thalamic ventral-Oralis complex/rostral zona incerta deep brain stimulation for midline tremor. J Neurol 2024; 271:6628-6638. [PMID: 39126514 PMCID: PMC11447151 DOI: 10.1007/s00415-024-12619-3] [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: 03/31/2024] [Revised: 06/20/2024] [Accepted: 07/30/2024] [Indexed: 08/12/2024]
Abstract
BACKGROUND Midline Tremor is defined as an isolated or combined tremor that affects the neck, trunk, jaw, tongue, and/or voice and could be part of Essential Tremor (ET), or dystonic tremor. The clinical efficacy of deep brain stimulation for Midline Tremor has been rarely reported. The Ventral Intermediate Nucleus and Globus Pallidus Internus are the preferred targets, but with variable outcomes. Thalamic Ventral-Oralis (VO) complex and Zona Incerta (ZI) are emerging targets for tremor control in various etiologies. OBJECTIVE To report on neuroradiological, neurophysiological targeting and long-term efficacy of thalamic Ventral-Oralis complex and Zona Incerta deep brain stimulation in Midline Tremor. METHODS Three patients (two males and one female) with Midline Tremor in dystonic syndromes were recruited for this open-label study. Clinical, surgical, neurophysiological intraoperative testing and long-term follow-up data are reported. RESULTS Intraoperative testing and reconstruction of volume of tissue activated confirmed the position of the electrodes in the area stimulated between the thalamic Ventral-Oralis complex and Zona Incerta in all patients. All three patients showed optimal control of both tremor and dystonic features at short-term (6 months) and long-term follow-up (up to 6 years). No adverse events occurred. CONCLUSION In the syndromes of Midline Tremor of various origins, the best target for DBS might be difficult to identify. Our results showed that thalamic Ventral-Oralis complex/Zona Incerta may be a viable and safe option even in specific forms of tremor with axial distribution.
Collapse
Affiliation(s)
- Alba Scerrati
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
- Neurosurgery Department, S. Anna University Hospital of Ferrara, Ferrara, Italy
| | - Andrea Gozzi
- Neurology Department, S. Anna University Hospital of Ferrara, Via Aldo Moro 8, 44124, Ferrara, Italy.
- Department of Neuroscience and Rehabilitation, University of Ferrara, Ferrara, Italy, via Aldo Moro 8, 44124.
| | - Michele Alessandro Cavallo
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
- Neurosurgery Department, S. Anna University Hospital of Ferrara, Ferrara, Italy
| | - Giorgio Mantovani
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
- Neurosurgery Department, S. Anna University Hospital of Ferrara, Ferrara, Italy
| | - Pietro Antenucci
- Neurology Department, S. Anna University Hospital of Ferrara, Via Aldo Moro 8, 44124, Ferrara, Italy
- Department of Neuroscience and Rehabilitation, University of Ferrara, Ferrara, Italy, via Aldo Moro 8, 44124
| | - Chiara Angelini
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
- Neurosurgery Department, S. Anna University Hospital of Ferrara, Ferrara, Italy
| | - Jay Guido Capone
- Neurology Department, S. Anna University Hospital of Ferrara, Via Aldo Moro 8, 44124, Ferrara, Italy
| | - Pasquale De Bonis
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
- Neurosurgery Department, S. Anna University Hospital of Ferrara, Ferrara, Italy
| | - Francesca Morgante
- Neurosciences and Cell Biology Institute, Neuromodulation and Motor Control Section, St George's University of London, London, UK
| | - Vittorio Rispoli
- Neurology, Neuroscience Head Neck Department, University of Modena and Reggio Emilia, Modena, Italy
| | - Mariachiara Sensi
- Neurology Department, S. Anna University Hospital of Ferrara, Via Aldo Moro 8, 44124, Ferrara, Italy
| |
Collapse
|
|
4
|
Saluja S, Qiu L, Wang AR, Campos G, Seilheimer R, McNab JA, Haber SN, Barbosa DAN, Halpern CH. Diffusion Magnetic Resonance Imaging Tractography Guides Investigation of the Zona Incerta: A Novel Target for Deep Brain Stimulation. Biol Psychiatry 2024; 96:445-454. [PMID: 38401802 PMCID: PMC11338738 DOI: 10.1016/j.biopsych.2024.02.1004] [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: 08/05/2023] [Revised: 02/02/2024] [Accepted: 02/16/2024] [Indexed: 02/26/2024]
Abstract
BACKGROUND The zona incerta (ZI) is a subcortical structure primarily investigated in rodents that is implicated in various behaviors, ranging from motor control to survival-associated activities, partly due to its integration in multiple neural circuits. In the current study, we used diffusion magnetic resonance imaging tractography to segment the ZI and gain insight into its connectivity in various circuits in humans. METHODS We performed probabilistic tractography in 7T diffusion MRI on 178 participants from the Human Connectome Project to validate the ZI's anatomical subdivisions and their respective tracts. K-means clustering segmented the ZI based on each voxel's connectivity profile. We further characterized the connections of each ZI subregion using probabilistic tractography with each subregion as a seed. RESULTS We identified 2 dominant clusters that delineated the whole ZI into rostral and caudal subregions. The caudal ZI primarily connected with motor regions, while the rostral ZI received a topographic distribution of projections from prefrontal areas, notably the anterior cingulate and medial prefrontal cortices. We generated a probabilistic ZI atlas that was registered to a patient-participant's magnetic resonance imaging scan for placement of stereoencephalographic leads for electrophysiology-guided deep brain stimulation to treat their obsessive-compulsive disorder. Rostral ZI stimulation improved the patient's core symptoms (mean improvement 21%). CONCLUSIONS We present a tractography-based atlas of the rostral and caudal ZI subregions constructed using high-resolution diffusion magnetic resonance imaging from 178 healthy participants. Our work provides an anatomical foundation to explore the rostral ZI as a novel target for deep brain stimulation to treat refractory obsessive-compulsive disorder and other disorders associated with dysfunctional reward circuitry.
Collapse
Affiliation(s)
- Sabir Saluja
- Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Liming Qiu
- Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Allan R Wang
- Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Gustavo Campos
- Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Robert Seilheimer
- Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Jennifer A McNab
- Department of Radiology, Stanford University School of Medicine, Stanford, California
| | - Suzanne N Haber
- Department of Pharmacology & Physiology, University of Rochester School of Medicine and Dentistry, Rochester, New York; Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts
| | - Daniel A N Barbosa
- Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
| | - Casey H Halpern
- Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Surgery, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania.
| |
Collapse
|
|
5
|
Jiang Z, He M, Young C, Cai J, Xu Y, Jiang Y, Li H, Yang M, Tong Q. Dopaminergic Neurons in Zona Incerta Drives Appetitive Self-Grooming. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2308974. [PMID: 39099402 PMCID: PMC11422805 DOI: 10.1002/advs.202308974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 07/07/2024] [Indexed: 08/06/2024]
Abstract
Dopaminergic (DA) neurons are known to play a key role in controlling behaviors. While DA neurons in other brain regions are extensively characterized, those in zona incerta (ZITH or A13) receive much less attention and their function remains to be defined. Here it is shown that optogenetic stimulation of these neurons elicited intensive self-grooming behaviors and promoted place preference, which can be enhanced by training but cannot be converted into contextual memory. Interestingly, the same stimulation increased DA release to periaqueductal grey (PAG) neurons and local PAG antagonism of DA action reduced the elicited self-grooming. In addition, A13 neurons increased their activity in response to various external stimuli and during natural self-grooming episodes. Finally, monosynaptic retrograde tracing showed that the paraventricular hypothalamus represents one of the major upstream brain regions to A13 neurons. Taken together, these results reveal that A13 neurons are one of the brain sites that promote appetitive self-grooming involving DA release to the PAG.
Collapse
Affiliation(s)
- Zhiying Jiang
- The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
| | - Michelle He
- The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
- Summer Undergraduate Research Program, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
- Sargent College of Health and Rehabilitation Sciences, Boston University, Boston, MA, 02215, USA
| | - Claire Young
- The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
| | - Jing Cai
- The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
- MD Anderson Cancer Center & UTHealth Graduate School for Biomedical Sciences, University of Texas Health Science at Houston, Houston, TX, 77030, USA
| | - Yuanzhong Xu
- The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
| | - Yanyan Jiang
- The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
| | - Hongli Li
- The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
| | - Maojie Yang
- The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
| | - Qingchun Tong
- The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
- MD Anderson Cancer Center & UTHealth Graduate School for Biomedical Sciences, University of Texas Health Science at Houston, Houston, TX, 77030, USA
| |
Collapse
|
|
6
|
Tong Y, Cho S, Coenen VA, Döbrössy MD. Input-output relation of midbrain connectomics in a rodent model of depression. J Affect Disord 2024; 345:443-454. [PMID: 37890539 DOI: 10.1016/j.jad.2023.10.124] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 09/13/2023] [Accepted: 10/18/2023] [Indexed: 10/29/2023]
Abstract
BACKGROUND The symptoms associated with depression are believed to arise from disruptions in information processing across brain networks. The ventral tegmental area (VTA) influences reward-based behavior, motivation, addiction, and psychiatric disorders, including depression. Deep brain stimulation (DBS) of the medial forebrain bundle (MFB), is an emerging therapy for treatment-resistant depression. Understanding the depression associated anatomical networks crucial for comprehending its antidepressant effects. METHODS Flinders Sensitive Line (FSL), a rodent model of depression and Sprague-Dawley rats (n = 10 each) were used in this study. We used monosynaptic tracing to map inputs of VTA efferent neurons: VTA-to-NAc nucleus accumbens (NAc) (both core and shell) and VTA-to-prefrontal cortex (PFC). Quantitative analysis explored afferent diversity and strengths. RESULTS VTA efferent neurons receive a variety of afferents with varying input weights and predominant neuromodulatory representation. Notably, NAc-core projecting VTA neurons showed stronger afferents from dorsal raphe, while NAc shell-projecting VTA neurons displayed lower input strengths from cortex, thalamus, zona incerta and pretectal area in FSL rats. NAc shell-projecting VTA neurons showed the most difference in connectivity across the experimental groups. LIMITATIONS Lack of functional properties of the anatomical connections is the major limitation of this study. Incomplete labeling and the cytotoxicity of the rabies virus should be made aware of. CONCLUSIONS These findings provide the first characterization of inputs to different VTA ascending projection neurons, shedding light on critical differences in the connectome of the midbrain-forebrain system. Moreover, these differences support potential network effects of these circuits in the context of MFB DBS neuromodulation for depression.
Collapse
Affiliation(s)
- Y Tong
- Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, University Hospital Freiburg, 79106 Freiburg, Germany; Department of Stereotactic and Functional Neurosurgery, University Hospital Freiburg, 79106 Freiburg, Germany
| | - S Cho
- Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, University Hospital Freiburg, 79106 Freiburg, Germany; Department of Stereotactic and Functional Neurosurgery, University Hospital Freiburg, 79106 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany
| | - V A Coenen
- Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, University Hospital Freiburg, 79106 Freiburg, Germany; Department of Stereotactic and Functional Neurosurgery, University Hospital Freiburg, 79106 Freiburg, Germany; Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; Center for Basics in Neuromodulation, University of Freiburg, 79106 Freiburg, Germany; IMBIT (Institute for Machine-Brain Interfacing Technology), University of Freiburg, 79110 Freiburg, Germany
| | - M D Döbrössy
- Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, University Hospital Freiburg, 79106 Freiburg, Germany; Department of Stereotactic and Functional Neurosurgery, University Hospital Freiburg, 79106 Freiburg, Germany; Center for Basics in Neuromodulation, University of Freiburg, 79106 Freiburg, Germany.
| |
Collapse
|
|
7
|
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.
Collapse
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.
| |
Collapse
|
|
8
|
Chen F, Qian J, Cao Z, Li A, Cui J, Shi L, Xie J. Chemogenetic and optogenetic stimulation of zona incerta GABAergic neurons ameliorates motor impairment in Parkinson's disease. iScience 2023; 26:107149. [PMID: 37416450 PMCID: PMC10319825 DOI: 10.1016/j.isci.2023.107149] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 04/26/2023] [Accepted: 06/12/2023] [Indexed: 07/08/2023] Open
Abstract
Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra and leads to progressive motor dysfunction. While studies have focused on the basal ganglia network, recent evidence suggests neuronal systems outside the basal ganglia are also related to PD pathogenesis. The zona incerta (ZI) is a predominantly inhibitory subthalamic region for global behavioral modulation. This study investigates the role of GABAergic neurons in the ZI in a mouse model of 6-hydroxydopamine (6-OHDA)-induced PD. First, we found a decrease in GABA-positive neurons in the ZI, and then the mice used chemogenetic/optogenetic stimulation to activate or inhibit GABAergic neurons. The motor performance of PD mice was significantly improved by chemogenetic/optogenetic activation of GABAergic neurons, and repeated chemogenetic activation of ZI GABAergic neurons increased the dopamine content in the striatum. Our work identifies the role of ZI GABAergic neurons in regulating motor behaviors in 6-OHDA-lesioned PD model mice.
Collapse
Affiliation(s)
- Fenghua Chen
- Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, School of Basic Medicine, Qingdao University, Qingdao, China
- Institute of Brain Science and Disease, Qingdao University, Qingdao, China
| | - Junliang Qian
- Institute of Brain Science and Disease, Qingdao University, Qingdao, China
| | - Zhongkai Cao
- Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, School of Basic Medicine, Qingdao University, Qingdao, China
- Institute of Brain Science and Disease, Qingdao University, Qingdao, China
| | - Ang Li
- Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, School of Basic Medicine, Qingdao University, Qingdao, China
- Institute of Brain Science and Disease, Qingdao University, Qingdao, China
| | - Juntao Cui
- Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, School of Basic Medicine, Qingdao University, Qingdao, China
- Institute of Brain Science and Disease, Qingdao University, Qingdao, China
| | - Limin Shi
- Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, School of Basic Medicine, Qingdao University, Qingdao, China
- Institute of Brain Science and Disease, Qingdao University, Qingdao, China
| | - Junxia Xie
- Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, School of Basic Medicine, Qingdao University, Qingdao, China
- Institute of Brain Science and Disease, Qingdao University, Qingdao, China
| |
Collapse
|
|
9
|
Ma FZ, Liu DF, Yang AC, Zhang K, Meng FG, Zhang JG, Liu HG. Application of the robot-assisted implantation in deep brain stimulation. Front Neurorobot 2022; 16:996685. [PMID: 36531913 PMCID: PMC9755501 DOI: 10.3389/fnbot.2022.996685] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 11/21/2022] [Indexed: 08/15/2023] Open
Abstract
INTRODUCTION This work aims to assess the accuracy of robotic assistance guided by a videometric tracker in deep brain stimulation (DBS). METHODS We retrospectively reviewed a total of 30 DBS electrode implantations, assisted by the Remebot robotic system, with a novel frameless videometric registration workflow. Then we selected 30 PD patients who used stereotactic frame surgery to implant electrodes during the same period. For each electrode, accuracy was assessed using radial and axial error. RESULTS The average radial error of the robot-assisted electrode implantation was 1.28 ± 0.36 mm, and the average axial error was 1.20 ± 0.40 mm. No deaths or associated hemorrhages, infections or poor incision healing occurred. CONCLUSION Robot-assisted implantation guided by a videometric tracker is accurate and safe.
Collapse
Affiliation(s)
- Fang-Zhou Ma
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - De-Feng Liu
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - An-Chao Yang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Kai Zhang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Fan-Gang Meng
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Jian-Guo Zhang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Neurostimulation, Beijing, China
| | - Huan-Guang Liu
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| |
Collapse
|
|
10
|
Farzinpour Z, Liu A, Cao P, Mao Y, Zhang Z, Jin Y. Microglial Engulfment of Spines in the Ventral Zona Incerta Regulates Anxiety-Like Behaviors in a Mouse Model of Acute Pain. Front Cell Neurosci 2022; 16:898346. [PMID: 35910255 PMCID: PMC9337222 DOI: 10.3389/fncel.2022.898346] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 06/17/2022] [Indexed: 12/20/2022] Open
Abstract
Although activation of microglial cells is critical in developing brain disorders, their role in anxiety-like behaviors in pain is still vague. This study indicates that alteration of microglia’s neuronal spine engulfment capacity in ventral zona incerta (ZIV) leads to significant pain and anxiety-like behaviors in mice 1-day post-injection of Complete Freud’s Adjuvant (CFA1D). Performing whole-cell patch-clamp recordings in GABAergic neurons in the ZIV (ZIVGABA) in brain slices, we observed decreased activity in ZIvGABA and reduced frequency of the miniature excitatory postsynaptic currents (mEPSCs) in ZIVGABA of CFA1D mice compared with the saline1D mice. Besides, chemogenetic activation of ZIVGABA significantly relieved pain and anxiety-like behaviors in CFA1D mice. Conversely, in naïve mice, chemogenetic inhibition of ZIVGABA induced pain and anxiety-like behaviors. Interestingly, we found changes in the density and morphology of ZIVMicroglia and increased microglial engulfment of spines in ZIV of CFA1D mice. Furthermore, pain sensitization and anxiety-like behaviors were reversed when the ZIVMicroglia of CFA1D-treated mice were chemically inhibited by intra-ZIV minocycline injection, accompanied by the recovery of decreased ZIVGABA excitability. Conclusively, our results provide novel insights that dysregulation of microglial engulfment capacity encodes maladaptation of ZIVGABA, thus promoting the development of anxiety-like behaviors in acute pain.
Collapse
Affiliation(s)
- Zahra Farzinpour
- Department of Anesthesiology and Pain Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - An Liu
- Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Peng Cao
- Department of Anesthesiology and Pain Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Yu Mao
- Department of Anesthesiology and Pain Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Zhi Zhang
- Department of Anesthesiology and Pain Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
- *Correspondence: Zhi Zhang,
| | - Yan Jin
- Stroke Center and Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
- Yan Jin,
| |
Collapse
|
|
11
|
Kratter IH, Jorge A, Feyder MT, Whiteman AC, Chang YF, Henry LC, Karp JF, Richardson RM. Depression history modulates effects of subthalamic nucleus topography on neuropsychological outcomes of deep brain stimulation for Parkinson's disease. Transl Psychiatry 2022; 12:213. [PMID: 35624103 PMCID: PMC9142573 DOI: 10.1038/s41398-022-01978-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 05/10/2022] [Accepted: 05/17/2022] [Indexed: 11/09/2022] Open
Abstract
Patients with psychiatric symptoms, such as depression, anxiety, and visual hallucinations, may be at increased risk for adverse effects following deep brain stimulation of the subthalamic nucleus for Parkinson's disease, but there have been relatively few studies of associations between locations of chronic stimulation and neuropsychological outcomes. We sought to determine whether psychiatric history modulates associations between stimulation location within the subthalamic nucleus and postoperative affective and cognitive changes. We retrospectively identified 42 patients with Parkinson's disease who received bilateral subthalamic nucleus deep brain stimulation and who completed both pre- and postoperative neuropsychological testing. Active stimulation contacts were localized in MNI space using Lead-DBS software. Linear discriminant analysis identified vectors maximizing variance in postoperative neuropsychological changes, and Pearson's correlations were used to assess for linear relationships. Stimulation location was associated with postoperative change for only 3 of the 18 neuropsychological measures. Variation along the superioinferior (z) axis was most influential. Constraining the analysis to patients with a history of depression revealed 10 measures significantly associated with active contact location, primarily related to location along the anterioposterior (y) axis and with worse outcomes associated with more anterior stimulation. Analysis of patients with a history of anxiety revealed 5 measures with location-associated changes without a predominant axis. History of visual hallucinations was not associated with significant findings. Our results suggest that a history of depression may influence the relationship between active contact location and neuropsychological outcomes following subthalamic nucleus deep brain stimulation. These patients may be more sensitive to off-target (nonmotor) stimulation.
Collapse
Affiliation(s)
- Ian H Kratter
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
- Brain Modulation Laboratory, Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA, 94305, USA.
| | - Ahmed Jorge
- Brain Modulation Laboratory, Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
- University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Michael T Feyder
- Brain Modulation Laboratory, Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Ashley C Whiteman
- Brain Modulation Laboratory, Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Yue-Fang Chang
- Brain Modulation Laboratory, Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Luke C Henry
- Brain Modulation Laboratory, Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Jordan F Karp
- Department of Psychiatry, College of Medicine, University of Arizona, Tucson, AZ, USA
| | - R Mark Richardson
- Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| |
Collapse
|
|
12
|
Baumgartner AJ, Thompson JA, Kern DS, Ojemann SG. Novel targets in deep brain stimulation for movement disorders. Neurosurg Rev 2022; 45:2593-2613. [PMID: 35511309 DOI: 10.1007/s10143-022-01770-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 12/01/2021] [Accepted: 03/08/2022] [Indexed: 12/26/2022]
Abstract
The neurosurgical treatment of movement disorders, primarily via deep brain stimulation (DBS), is a rapidly expanding and evolving field. Although conventional targets including the subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) for Parkinson's disease and ventral intermediate nucleus of the thalams (VIM) for tremor provide substantial benefit in terms of both motor symptoms and quality of life, other targets for DBS have been explored in an effort to maximize clinical benefit and also avoid undesired adverse effects associated with stimulation. These novel targets primarily include the rostral zona incerta (rZI), caudal zona incerta (cZI)/posterior subthalamic area (PSA), prelemniscal radiation (Raprl), pedunculopontine nucleus (PPN), substantia nigra pars reticulata (SNr), centromedian/parafascicular (CM/PF) nucleus of the thalamus, nucleus basalis of Meynert (NBM), dentato-rubro-thalamic tract (DRTT), dentate nucleus of the cerebellum, external segment of the globus pallidus (GPe), and ventral oralis (VO) complex of the thalamus. However, reports of outcomes utilizing these targets are scattered and disparate. In order to provide a comprehensive resource for researchers and clinicians alike, we have summarized the existing literature surrounding these novel targets, including rationale for their use, neurosurgical techniques where relevant, outcomes and adverse effects of stimulation, and future directions for research.
Collapse
Affiliation(s)
| | - John A Thompson
- Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA
- University of Colorado Hospital, 12631 East 17th Avenue, PO Box 6511, Aurora, CO, 80045, USA
| | - Drew S Kern
- Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA
- University of Colorado Hospital, 12631 East 17th Avenue, PO Box 6511, Aurora, CO, 80045, USA
| | - Steven G Ojemann
- Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA.
- University of Colorado Hospital, 12631 East 17th Avenue, PO Box 6511, Aurora, CO, 80045, USA.
| |
Collapse
|
|
13
|
de Roquemaurel A, Wirth T, Vijiaratnam N, Ferreira F, Zrinzo L, Akram H, Foltynie T, Limousin P. Stimulation Sweet Spot in Subthalamic Deep Brain Stimulation - Myth or Reality? A Critical Review of Literature. Stereotact Funct Neurosurg 2021; 99:425-442. [PMID: 34120117 DOI: 10.1159/000516098] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 03/23/2021] [Indexed: 11/19/2022]
Abstract
INTRODUCTION While deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been extensively used for more than 20 years in Parkinson's disease (PD), the optimal area of stimulation to relieve motor symptoms remains elusive. OBJECTIVE We aimed at localizing the sweet spot within the subthalamic region by performing a systematic review of the literature. METHOD PubMed database was searched for published studies exploring optimal stimulation location for STN DBS in PD, published between 2000 and 2019. A standardized assessment procedure based on methodological features was applied to select high-quality publications. Studies conducted more than 3 months after the DBS procedure, employing lateralized scores and/or stimulation condition, and reporting the volume of tissue activated or the position of the stimulating contact within the subthalamic region were considered in the final analysis. RESULTS Out of 439 references, 24 were finally retained, including 21 studies based on contact location and 3 studies based on volume of tissue activated (VTA). Most studies (all VTA-based studies and 13 of the 21 contact-based studies) suggest the superior-lateral STN and the adjacent white matter as the optimal sites for stimulation. Remaining contact-based studies were either inconclusive (5/21), favoured the caudal zona incerta (1/21), or suggested a better outcome of STN stimulation than adjacent white matter stimulation (2/21). CONCLUSION Using a standardized methodological approach, our review supports the presence of a sweet spot located within the supero-lateral STN and extending to the adjacent white matter.
Collapse
Affiliation(s)
- Alexis de Roquemaurel
- Unit of Functional Neurosurgery, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, United Kingdom
| | - Thomas Wirth
- Unit of Functional Neurosurgery, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, United Kingdom.,Neurology department, Strasbourg University Hospital, Strasbourg, France.,INSERM-U964/CNRS-UMR7104/University of Strasbourg, Illkirch-Graffenstaden, France
| | - Nirosen Vijiaratnam
- Unit of Functional Neurosurgery, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, United Kingdom
| | - Francisca Ferreira
- Unit of Functional Neurosurgery, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, United Kingdom
| | - Ludvic Zrinzo
- Unit of Functional Neurosurgery, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, United Kingdom
| | - Harith Akram
- Unit of Functional Neurosurgery, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, United Kingdom
| | - Thomas Foltynie
- Unit of Functional Neurosurgery, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, United Kingdom
| | - Patricia Limousin
- Unit of Functional Neurosurgery, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, United Kingdom
| |
Collapse
|
|
14
|
Thaker AA, Reddy KM, Thompson JA, Gerecht PD, Brown MS, Abosch A, Ojemann SG, Kern DS. Coronal Gradient Echo MRI to Visualize the Zona Incerta for Deep Brain Stimulation Targeting in Parkinson's Disease. Stereotact Funct Neurosurg 2021; 99:443-450. [PMID: 33902054 DOI: 10.1159/000515772] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 03/10/2021] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Deep brain stimulation of the zona incerta is effective at treating tremor and other forms of parkinsonism. However, the structure is not well visualized with standard MRI protocols making direct surgical targeting unfeasible and contributing to inconsistent clinical outcomes. In this study, we applied coronal gradient echo MRI to directly visualize the rostral zona incerta in Parkinson's disease patients to improve targeting for deep brain stimulation. METHODS We conducted a prospective study to optimize and evaluate an MRI sequence to visualize the rostral zona incerta in patients with Parkinson's disease (n = 31) and other movement disorders (n = 13). We performed a contrast-to-noise ratio analysis of specific regions of interest to quantitatively assess visual discrimination of relevant deep brain structures in the optimized MRI sequence. Regions of interest were independently assessed by 2 neuroradiologists, and interrater reliability was assessed. RESULTS Rostral zona incerta and subthalamic nucleus were well delineated in our 5.5-min MRI sequence, indicated by excellent interrater agreement between neuroradiologists for region-of-interest measurements (>0.90 intraclass coefficient). Mean contrast-to-noise ratio was high for both rostral zona incerta (6.39 ± 3.37) and subthalamic nucleus (17.27 ± 5.61) relative to adjacent white matter. There was no significant difference between mean signal intensities or contrast-to-noise ratio for Parkinson's and non-Parkinson's patients for either structure. DISCUSSION/CONCLUSION Our optimized coronal gradient echo MRI sequence delineates subcortical structures relevant to traditional and novel deep brain stimulation targets, including the zona incerta, with high contrast-to-noise. Future studies will prospectively apply this sequence to surgical planning and postimplantation outcomes.
Collapse
Affiliation(s)
- Ashesh A Thaker
- Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Kartik M Reddy
- Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - John A Thompson
- Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.,Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Pamela David Gerecht
- Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Mark S Brown
- Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Aviva Abosch
- Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.,Department of Neurosurgery, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Steven G Ojemann
- Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Drew S Kern
- Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.,Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| |
Collapse
|
|
15
|
Ossowska K. Zona incerta as a therapeutic target in Parkinson's disease. J Neurol 2020; 267:591-606. [PMID: 31375987 PMCID: PMC7035310 DOI: 10.1007/s00415-019-09486-8] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 07/25/2019] [Accepted: 07/26/2019] [Indexed: 12/21/2022]
Abstract
The zona incerta has recently become an important target for deep-brain stimulation (DBS) in Parkinson's disease (PD). The present review summarizes clinical, animal and anatomical data which have indicated an important role of this structure in PD, and discusses potential mechanisms involved in therapeutic effects of DBS. Animal studies have suggested initially some role of neurons as well as GABAergic and glutamatergic receptors of the zona incerta in locomotion and generation of PD signs. Anatomical data have indicated that thanks to its multiple interconnections with the basal ganglia, thalamus, cerebral cortex, brainstem, spinal cord and cerebellum, the zona incerta is an important link in a neuronal chain transmitting impulses involved in PD pathology. Finally, clinical studies have shown that DBS of this structure alleviates parkinsonian bradykinesia, muscle rigidity and tremor. DBS of caudal zona incerta seemed to be the most effective therapeutic intervention, especially with regard to reduction of PD tremor as well as other forms of tremor.
Collapse
Affiliation(s)
- Krystyna Ossowska
- Department of Neuropsychopharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna St, 31-343, Kraków, Poland.
| |
Collapse
|
|
16
|
Becker R, Gass N, Kußmaul L, Schmid B, Scheuerer S, Schnell D, Dorner-Ciossek C, Weber-Fahr W, Sartorius A. NMDA receptor antagonists traxoprodil and lanicemine improve hippocampal-prefrontal coupling and reward-related networks in rats. Psychopharmacology (Berl) 2019; 236:3451-3463. [PMID: 31267156 DOI: 10.1007/s00213-019-05310-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 06/18/2019] [Indexed: 12/13/2022]
Abstract
RATIONALE The N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine is known to have not only a rapid antidepressant effect but also dissociative side effects. Traxoprodil and lanicemine, also NMDA antagonists, are candidate antidepressant drugs with fewer side effects. OBJECTIVES In order to understand their mechanism of action, we investigated the acute effects of traxoprodil and lanicemine on brain connectivity using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS Functional connectivity (FC) alterations were examined using interregional correlation networks. Graph theoretical methods were used for whole brain network analysis. As interest in NMDAR antagonists as potential antidepressants was triggered by the antidepressant effect of ketamine, results were compared to previous findings from our ketamine studies. RESULTS Similar to ketamine but to a smaller extent, traxoprodil increased hippocampal-prefrontal (Hc-PFC) coupling. Unlike ketamine, traxoprodil decreased connectivity within the PFC. Lanicemine had no effect on these properties. The improvement of Hc-PFC coupling corresponds well to clinical result, showing ketamine to have a greater antidepressant effect than traxoprodil, while lanicemine has a weak and transient effect. Connectivity changes overlapping between the drugs as well as alterations of local network properties occurred mostly in reward-related regions. CONCLUSION The antidepressant effect of NMDA antagonists appears to be associated with enhanced Hc-PFC coupling. The effects on local network properties and regional connectivity suggest that improvement of reward processing might also be important for understanding the mechanisms underlying the antidepressant effects of these drugs.
Collapse
Affiliation(s)
- Robert Becker
- Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159, Mannheim, Germany.
| | - Natalia Gass
- Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159, Mannheim, Germany
| | - Lothar Kußmaul
- Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany
| | - Bernhard Schmid
- Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany
| | | | - David Schnell
- Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany
| | | | - Wolfgang Weber-Fahr
- Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159, Mannheim, Germany
| | - Alexander Sartorius
- Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159, Mannheim, Germany.,Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| |
Collapse
|
|
17
|
Koeglsperger T, Palleis C, Hell F, Mehrkens JH, Bötzel K. Deep Brain Stimulation Programming for Movement Disorders: Current Concepts and Evidence-Based Strategies. Front Neurol 2019; 10:410. [PMID: 31231293 PMCID: PMC6558426 DOI: 10.3389/fneur.2019.00410] [Citation(s) in RCA: 134] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Accepted: 04/04/2019] [Indexed: 11/16/2022] Open
Abstract
Deep brain stimulation (DBS) has become the treatment of choice for advanced stages of Parkinson's disease, medically intractable essential tremor, and complicated segmental and generalized dystonia. In addition to accurate electrode placement in the target area, effective programming of DBS devices is considered the most important factor for the individual outcome after DBS. Programming of the implanted pulse generator (IPG) is the only modifiable factor once DBS leads have been implanted and it becomes even more relevant in cases in which the electrodes are located at the border of the intended target structure and when side effects become challenging. At present, adjusting stimulation parameters depends to a large extent on personal experience. Based on a comprehensive literature search, we here summarize previous studies that examined the significance of distinct stimulation strategies for ameliorating disease signs and symptoms. We assess the effect of adjusting the stimulus amplitude (A), frequency (f), and pulse width (pw) on clinical symptoms and examine more recent techniques for modulating neuronal elements by electrical stimulation, such as interleaving (Medtronic®) or directional current steering (Boston Scientific®, Abbott®). We thus provide an evidence-based strategy for achieving the best clinical effect with different disorders and avoiding adverse effects in DBS of the subthalamic nucleus (STN), the ventro-intermedius nucleus (VIM), and the globus pallidus internus (GPi).
Collapse
Affiliation(s)
- Thomas Koeglsperger
- Department of Neurology, Ludwig Maximilians University, Munich, Germany.,Department of Translational Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
| | - Carla Palleis
- Department of Neurology, Ludwig Maximilians University, Munich, Germany.,Department of Translational Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
| | - Franz Hell
- Department of Neurology, Ludwig Maximilians University, Munich, Germany.,Graduate School of Systemic Neurosciences, Ludwig-Maximilians-Universität München, Martinsried, Germany
| | - Jan H Mehrkens
- Department of Neurosurgery, Ludwig Maximilians University, Munich, Germany
| | - Kai Bötzel
- Department of Neurology, Ludwig Maximilians University, Munich, Germany
| |
Collapse
|
|
18
|
Abstract
Fear expressed toward threat-associated stimuli is an adaptive behavioral response. In contrast, the generalization of fear responses toward nonthreatening cues is a maladaptive and debilitating dimension of trauma- and anxiety-related disorders. Expressing fear to appropriate stimuli and suppressing fear generalization require integration of relevant sensory information and motor output. While thalamic and subthalamic brain regions play important roles in sensorimotor integration, very little is known about the contribution of these regions to the phenomenon of fear generalization. In this study, we sought to determine whether fear generalization could be modulated by the zona incerta (ZI), a subthalamic brain region that influences sensory discrimination, defensive responses, and retrieval of fear memories. To do so, we combined differential intensity-based auditory fear conditioning protocols in mice with C-FOS immunohistochemistry and designer receptors exclusively activated by designer drugs (DREADDs)-based manipulation of neuronal activity in the ZI. C-FOS immunohistochemistry revealed an inverse relationship between ZI activation and fear generalization: The ZI was less active in animals that generalized fear. In agreement with this relationship, chemogenetic inhibition of the ZI resulted in fear generalization, while chemogenetic activation of the ZI suppressed fear generalization. Furthermore, targeted stimulation of GABAergic cells in the ZI reduced fear generalization. To conclude, our data suggest that stimulation of the ZI could be used to treat fear generalization in the context of trauma- and anxiety-related disorders.
Collapse
|
|
19
|
Kern DS, Picillo M, Thompson JA, Sammartino F, di Biase L, Munhoz RP, Fasano A. Interleaving Stimulation in Parkinson's Disease, Tremor, and Dystonia. Stereotact Funct Neurosurg 2019; 96:379-391. [PMID: 30654368 DOI: 10.1159/000494983] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Accepted: 10/24/2018] [Indexed: 11/19/2022]
Abstract
BACKGROUND/AIMS Interleaving stimulation (ILS) in deep brain stimulation (DBS) provides individualized stimulation of 2 contacts delivered in alternating order. Currently, limited information on the utility of ILS exists. The aims of this study were to determine the practical applications and outcomes of ILS DBS in Parkinson's disease (PD), tremor, and dystonia. METHODS We performed a single-center, unblinded, retrospective chart review of all patients with DBS attempted on ILS at our referral center assessing for rationale and outcomes. RESULTS Fifty patients (PD, n = 27; tremor, n = 7; dystonia, n = 16 patients) tried ILS for 2 rationales: management of adverse effects (n = 29) and to improve clinical efficacy (n = 21). A total of 19 patients demonstrated improvement with ILS for adverse effect management predominately for the treatment of dyskinesias (n = 12). In the vast majority of dyskinetic patients, a contact added into the rostral zona incerta with ILS was performed. Nine out of 21 patients demonstrated improved clinical efficacy with ILS with all 6 PD patients who tried ILS for this rationale demonstrating benefit. CONCLUSIONS In PD, ILS provided benefits for dyskinesias and parkinsonism, with minimal improvement of other adverse effects. In tremor and dystonia, marginal effects in terms of mitigation of adverse effects and improvement of clinical outcomes were evident.
Collapse
Affiliation(s)
- Drew S Kern
- Movement Disorders Center, Department of Neurology, University of Colorado, Denver, Colorado, USA, .,Movement Disorders Center, Department of Neurosurgery, University of Colorado, Denver, Colorado, USA,
| | - Marina Picillo
- Center for Neurodegenerative Diseases (CEMAND), Department of Medicine and Surgery, Neuroscience Section, University of Salerno, Salerno, Italy
| | - John A Thompson
- Movement Disorders Center, Department of Neurosurgery, University of Colorado, Denver, Colorado, USA
| | - Francesco Sammartino
- Division of Neurosurgery, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada
| | - Lazzaro di Biase
- Neurology Unit, Campus Bio-Medico University, Rome, Italy.,Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
| | - Renato P Munhoz
- Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Division of Neurology, University of Toronto, Toronto, Ontario, Canada
| | - Alfonso Fasano
- Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Division of Neurology, University of Toronto, Toronto, Ontario, Canada.,Krembil Research Institute, Toronto, Ontario, Canada
| |
Collapse
|
|
20
|
Neudorfer C, Maarouf M. Neuroanatomical background and functional considerations for stereotactic interventions in the H fields of Forel. Brain Struct Funct 2017; 223:17-30. [DOI: 10.1007/s00429-017-1570-4] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Accepted: 11/13/2017] [Indexed: 11/29/2022]
|
|
21
|
Deep Brain Stimulation in Parkinson's Disease: New and Emerging Targets for Refractory Motor and Nonmotor Symptoms. PARKINSONS DISEASE 2017; 2017:5124328. [PMID: 28761773 PMCID: PMC5518514 DOI: 10.1155/2017/5124328] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/05/2017] [Revised: 05/12/2017] [Accepted: 06/06/2017] [Indexed: 12/30/2022]
Abstract
Parkinson's disease (PD) is a progressive neurodegenerative condition characterized by bradykinesia, tremor, rigidity, and postural instability (PI), in addition to numerous nonmotor manifestations. Many pharmacological therapies now exist to successfully treat PD motor symptoms; however, as the disease progresses, it often becomes challenging to treat with medications alone. Deep brain stimulation (DBS) has become a crucial player in PD treatment, particularly for patients who have disabling motor complications from medical treatment. Well-established DBS targets include the subthalamic nucleus (STN), the globus pallidus pars interna (GPi), and to a lesser degree the ventral intermediate nucleus (VIM) of the thalamus. Studies of alternative DBS targets for PD are ongoing, the majority of which have shown some clinical benefit; however, more carefully designed and controlled studies are needed. In the present review, we discuss the role of these new and emerging DBS targets in treating refractory axial motor symptoms and other motor and nonmotor symptoms (NMS).
Collapse
|
|
22
|
Sundstedt S, Holmén L, Rova E, Linder J, Nordh E, Olofsson K. Swallowing safety in Parkinson's disease after zona incerta deep brain stimulation. Brain Behav 2017. [PMID: 28638714 PMCID: PMC5474712 DOI: 10.1002/brb3.709] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
OBJECTIVES The objective of this study was to examine swallowing function in patients with Parkinson's disease before and after caudal zona incerta deep brain (cZI DBS) surgery. The aims were to examine the effect of cZI DBS on swallowing safety regarding liquid and solid food, as well as to identify the effect of cZI DBS on body mass index (BMI) and specific items from part II of the Unified Parkinson's Disease Rating Scale (UPDRS). MATERIALS AND METHODS The median age of the 14 patients was 57 years (range 46-71), with a median disease duration of 6 years (range 2-13). The present sample is an extension of a previous report, into which six additional patients have been added. Fiber endoscopic examinations of swallowing function, measures of BMI, and evaluation of UPDRS part II items were made before and 12 months after surgery, with and without activated DBS. RESULTS There were no significant changes due to cZI DBS regarding penetration/aspiration, pharyngeal residue or premature spillage (p > .05). Median BMI increased by +1.1 kg/m2 12 months after surgery (p = .01, r = .50). All reported specific symptoms from the UPDRS part II were slight or mild. A significant improvement regarding handling of utensils was seen 12 months postoperatively (p = .03, r = -.42). CONCLUSIONS Caudal zona incerta DBS was found not to have a negative impact on swallowing safety. A significant increase in postoperative weight was observed, and speech seemed to be slightly negatively affected, whereas handling of utensils was improved with cZI DBS.
Collapse
Affiliation(s)
- Stina Sundstedt
- Division of Otorhinolaryngology Department of Clinical Sciences Umeå University Umeå Sweden
| | - Lina Holmén
- Division of Speech and Language Pathology Department of Clinical Sciences Umeå University Umeå Sweden
| | - Elin Rova
- Division of Speech and Language Pathology Department of Clinical Sciences Umeå University Umeå Sweden
| | - Jan Linder
- Division of Neurology Department of Pharmacology and Clinical Neurosciences Umeå University Umeå Sweden
| | - Erik Nordh
- Division Neurophysiology Department of Pharmacology and Clinical Neurosciences Umeå University Umeå Sweden
| | - Katarina Olofsson
- Division of Otorhinolaryngology Department of Clinical Sciences Umeå University Umeå Sweden
| |
Collapse
|
|
23
|
Rossi PJ, Gunduz A, Okun MS. The Subthalamic Nucleus, Limbic Function, and Impulse Control. Neuropsychol Rev 2015; 25:398-410. [PMID: 26577509 DOI: 10.1007/s11065-015-9306-9] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2015] [Accepted: 11/08/2015] [Indexed: 12/16/2022]
Abstract
It has been well documented that deep brain stimulation (DBS) of the subthalamic nucleus (STN) to address some of the disabling motor symptoms of Parkinson's disease (PD) can evoke unintended effects, especially on non-motor behavior. This observation has catalyzed more than a decade of research concentrated on establishing trends and identifying potential mechanisms for these non-motor effects. While many issues remain unresolved, the collective result of many research studies and clinical observations has been a general recognition of the role of the STN in mediating limbic function. In particular, the STN has been implicated in impulse control and the related construct of valence processing. A better understanding of STN involvement in these phenomena could have important implications for treating impulse control disorders (ICDs). ICDs affect up to 40% of PD patients on dopamine agonist therapy and approximately 15% of PD patients overall. ICDs have been reported to be associated with STN DBS. In this paper we will focus on impulse control and review pre-clinical, clinical, behavioral, imaging, and electrophysiological studies pertaining to the limbic function of the STN.
Collapse
Affiliation(s)
- P Justin Rossi
- Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL, USA. .,Department of Neurology, University of Florida College of Medicine, HSC Box 100236, Gainesville, FL, 32610-0236, USA.
| | - Aysegul Gunduz
- J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA
| | - Michael S Okun
- Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL, USA
| |
Collapse
|
|
24
|
The Quantitative Measurement of Reversible Acute Depression after Subthalamic Deep Brain Stimulation in a Patient with Parkinson Disease. Case Rep Neurol Med 2015; 2015:165846. [PMID: 26090244 PMCID: PMC4450288 DOI: 10.1155/2015/165846] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Accepted: 04/30/2015] [Indexed: 12/04/2022] Open
Abstract
Background. Depression is the most commonly reported mood symptom affecting 2–8% of patients after deep brain stimulation (DBS). Usually, symptoms develop gradually; however there have been cases of reproducible events that the mood symptoms were elicited within seconds to minutes after stimulation and were immediately reversible upon cessation of the stimulus. In the current study, we applied a self-reported questionnaire to assess the patient's mood state. Objective. To objectively measure the reversible acute depression induced by DBS in a patient with Parkinson disease (PD). Methods. A statistically validated Spanish version of the Beck Depression Inventory Short Form (BDI-SF) was used. The questionnaire was administered three times. Results. The patient became acutely depressed within ninety seconds of monopolar stimulation on the right side. His symptoms resolved immediately after changing the setting to bipolar stimulation. The BDI-SF scores during stimulation off, on, and off again were 15, 19, and 6, respectively. Conclusions. The BDI-SF scores increased during stimulation and decreased after cessation. This is consistent with a reversible depressive state. The poststimulation BDI-SF score decreased to less than half of the baseline score. This may suggest that the depression was more severe than the patient was able to express during the stimulation.
Collapse
|
|
25
|
Satzer D, Maurer EW, Lanctin D, Guan W, Abosch A. Anatomic correlates of deep brain stimulation electrode impedance. J Neurol Neurosurg Psychiatry 2015; 86:398-403. [PMID: 24935985 DOI: 10.1136/jnnp-2013-307284] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
BACKGROUND The location of the optimal target for deep brain stimulation (DBS) of the subthalamic nucleus (STN) remains controversial. Electrode impedance affects tissue activation by DBS and has been found to vary by contact number, but no studies have examined association between impedance and anatomic location. OBJECTIVES To evaluate the relationship between electrode impedance and anatomic contact location, and to assess the clinical significance of impedance. METHODS We gathered retrospective impedance data from 101 electrodes in 73 patients with Parkinson's disease. We determined contact location using microelectrode recording (MER) and high-field 7T MRI, and assessed the relationship between impedance and contact location. RESULTS For contact location as assessed via MER, impedance was significantly higher for contacts in STN, at baseline (111 Ω vs STN border, p=0.03; 169 Ω vs white matter, p<0.001) and over time (90 Ω vs STN border, p<0.001; 54 Ω vs white matter, p<0.001). Over time, impedance was lowest in contacts situated at STN border (p=0.03). Impedance did not vary by contact location as assessed via imaging. Location determination was 75% consistent between MER and imaging. Impedance was inversely related to absolute symptom reduction during stimulation (-2.5 motor portion of the Unified Parkinson's Disease Rating Scale (mUPDRS) points per 1000 Ω, p=0.01). CONCLUSIONS In the vicinity of DBS electrodes chronically implanted in STN, impedance is lower at the rostral STN border and in white matter, than in STN. This finding suggests that current reaches white matter fibres more readily than neuronal cell bodies in STN, which may help explain anatomic variation in stimulation efficacy.
Collapse
Affiliation(s)
- David Satzer
- Department of Neurosurgery, University of Minnesota, Minneapolis, Minnesota, USA
| | - Eric W Maurer
- Department of Neurosurgery, University of Minnesota, Minneapolis, Minnesota, USA
| | - David Lanctin
- Department of Neurosurgery, University of Minnesota, Minneapolis, Minnesota, USA
| | - Weihua Guan
- Department of Biostatistics, University of Minnesota, Minneapolis, Minnesota, USA
| | - Aviva Abosch
- Department of Neurosurgery, University of Minnesota, Minneapolis, Minnesota, USA Department of Neurosurgery, University of Colorado, Denver, Colorado, USA
| |
Collapse
|
|
26
|
Eisenstein SA, Koller JM, Black KD, Campbell MC, Lugar HM, Ushe M, Tabbal SD, Karimi M, Hershey T, Perlmutter JS, Black KJ. Functional anatomy of subthalamic nucleus stimulation in Parkinson disease. Ann Neurol 2014; 76:279-95. [PMID: 24953991 PMCID: PMC4172323 DOI: 10.1002/ana.24204] [Citation(s) in RCA: 98] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2014] [Revised: 06/17/2014] [Accepted: 06/17/2014] [Indexed: 12/19/2022]
Abstract
OBJECTIVE We developed a novel method to map behavioral effects of deep brain stimulation (DBS) across a 3-dimensional brain region and to assign statistical significance after stringent type I error correction. This method was applied to behavioral changes in Parkinson disease (PD) induced by subthalamic nucleus (STN) DBS to determine whether these responses depended on anatomical location of DBS. METHODS Fifty-one PD participants with STN DBS were evaluated off medication, with DBS off and during unilateral STN DBS with clinically optimized settings. Dependent variables included DBS-induced changes in Unified Parkinson Disease Rating Scale (UPDRS) subscores, kinematic measures of bradykinesia and rigidity, working memory, response inhibition, mood, anxiety, and akathisia. Weighted t tests at each voxel produced p images showing where DBS most significantly affected each dependent variable based on outcomes of participants with nearby DBS. Finally, a permutation test computed the probability that this p image indicated significantly different responses based on stimulation site. RESULTS Most motor variables improved with DBS anywhere in the STN region, but several motor, cognitive, and affective responses significantly depended on precise location stimulated, with peak p values in superior STN/zona incerta (quantified bradykinesia), dorsal STN (mood, anxiety), and inferior STN/substantia nigra (UPDRS tremor, working memory). INTERPRETATION Our method identified DBS-induced behavioral changes that depended significantly on DBS site. These results do not support complete functional segregation within STN, because movement improved with DBS throughout, and mood improved with dorsal STN DBS. Rather, findings support functional convergence of motor, cognitive, and limbic information in STN.
Collapse
Affiliation(s)
- Sarah A Eisenstein
- Department of Psychiatry, Washington University in St Louis, St Louis, MO
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
27
|
A movable microelectrode array for chronic basal ganglia single-unit electrocorticogram co-recording in freely behaving rats. Neurol Sci 2014; 35:1429-39. [PMID: 24838541 DOI: 10.1007/s10072-014-1775-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2013] [Accepted: 02/20/2014] [Indexed: 10/25/2022]
Abstract
The basal ganglia-cortical circuits are important for information process to brain function. However, chronic recording of single-unit activities in the basal ganglia nucleus has not yet been well established. We present a movable bundled microwire array for chronic subthalamic nucleus (STN) single-unit electrocorticogram co-recording. The electrode assembly contains a screw-advanced microdrive and a microwire array. The array consists of a steel guide tube, five recording wires and one referenced wire which form the shape of a guiding hand, and one screw electrode for cortico-recording. The electrode can acquire stable cortex oscillation-driven STN firing units in rats under different behaving conditions for 8 weeks. We achieved satisfying signal-to-noise ratio, portions of cells retaining viability, and spike waveform similarities across the recording sections. Using this method, we investigated neural correlations of the basal ganglia-cortical circuits in different behaving conditions. This method will become a powerful tool for multi-region recording to study normal statements or movement disorders.
Collapse
|
|
28
|
Kerl HU, Gerigk L, Brockmann MA, Huck S, Al-Zghloul M, Groden C, Hauser T, Nagel AM, Nölte IS. Imaging for deep brain stimulation: The zona incerta at 7 Tesla. World J Radiol 2013; 5:5-16. [PMID: 23494089 PMCID: PMC3596566 DOI: 10.4329/wjr.v5.i1.5] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2012] [Revised: 10/24/2012] [Accepted: 01/21/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate different promising magnetic resonance imaging (MRI) methods at 7.0 Tesla (T) for the pre-stereotactic visualization of the zona incerta (ZI).
METHODS: Two neuroradiologists qualitatively and quantitatively examined T2-turbo spin-echo (T2-TSE), T1-weighted gradient-echo, as well as FLASH2D-T2Star and susceptibility-weighted imaging (SWI) for the visualization of the ZI at 7.0 T MRI. Delineation and image quality for the ZI were independently examined using a 6-scale grading system. Inter-rater reliability using Cohen’s kappa coefficient (κ) were assessed. Contrast-to-noise ratios (CNR), and signal-to-noise ratios (SNR) for the ZI were calculated for all sequences. Differences in delineation, SNR, and CNR between the sequences were statistically assessed using a paired t-test. For the anatomic validation the coronal FLASH2D-T2Star images were co-registered with a stereotactic atlas (Schaltenbrand-Wahren).
RESULTS: The rostral part of the ZI (rZI) could easily be identified and was best and reliably visualized in the coronal FLASH2D-T2Star images. The caudal part was not definable in any of the sequences. No major artifacts in the rZI were observed in any of the scans. FLASH2D-T2Star and SWI imaging offered significant higher CNR values for the rZI compared to T2-TSE images (P > 0.05). The co-registration of the coronal FLASH2D-T2Star images with the stereotactic atlas schema (Schaltenbrand-Wahren) confirmed the correct localization of the ZI in all cases.
CONCLUSION: FLASH2D-T2Star imaging (particularly coronal view) provides the reliable and currently optimal visualization of the rZI at 7.0 T. These results can facilitate a better and more precise targeting of the caudal part of the ZI than ever before.
Collapse
|
|
29
|
Visualisation of the zona incerta for deep brain stimulation at 3.0 Tesla. Clin Neuroradiol 2012; 22:55-68. [PMID: 22349435 DOI: 10.1007/s00062-012-0136-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2011] [Accepted: 01/27/2012] [Indexed: 12/23/2022]
Abstract
PURPOSE Deep-brain stimulation (DBS) of the zona incerta (ZI) has shown promising results for medication-refractory neurological disorders including Parkinson's disease (PD) and essential tremor (ET). The success of the intervention is indispensably dependent on the reliable visualisation of the ZI. The aim of the study was to evaluate different promising new magnetic resonance imaging (MRI) methods at 3.0 Tesla for pre-stereotactic visualisation of the ZI using a standard installation the protocol. METHODS MRI of nine healthy volunteers was acquired (T1-MPRAGE, T2-FLAIR, T2*-FLASH2D, T2-SPACE and susceptibility-weighted imaging (SWI). Image quality and visualisation of the ZI for each sequence were analysed independently by two neuroradiologists using a 6-point scale. For T2*-FLASH2D the axial, coronal and sagittal planes were compared. The delineation of the ZI versus the internal capsule, the subthalamic nucleus and the pallidofugal fibres was evaluated in all sequences and compared to T2-FLAIR using a paired t-test. Inter-rater reliability, contrast-to-noise ratios (CNR), and signal-to-noise ratios (SNR) for the ZI were computed. For illustration, coronal T2*-FLASH2D images were co-registered with the corresponding section schema of the Schaltenbrand-Wahren stereotactic atlas. RESULTS Only the rostral part of the ZI (rZI) could be identified. The rZI was best and reliably visualised in T2*-FLASH2D (particularly coronal orientation; p < 0.05). No major artifacts in the rZI were observed in any of the sequences. SWI, T2-SPACE, and T2*-FLASH imaging offered significant higher CNR values for the rZI compared to T2-FLAIR imaging using standard parameters. The co-registration of the coronal T2*-FLASH2D images projected the ZI clearly into the boundaries of the anatomical sections. CONCLUSIONS The delineation of the rZI is best possible in T2*-FLASH2D (particularly coronal view) using a standard installation protocol at 3.0 T. The caudal ZI could not be discerned in any of the sequences.
Collapse
|