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Blank E, Gilbert DL, Wu SW, Larsh T, Elmaghraby R, Liu R, Smith E, Westerkamp G, Liu Y, Horn PS, Greenstein E, Sweeney JA, Erickson CA, Pedapati EV. Accelerated Theta Burst Transcranial Magnetic Stimulation for Refractory Depression in Autism Spectrum Disorder. J Autism Dev Disord 2025; 55:940-954. [PMID: 38744742 PMCID: PMC11828798 DOI: 10.1007/s10803-024-06244-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/09/2024] [Indexed: 05/16/2024]
Abstract
PURPOSE Major depressive disorder (MDD) disproportionately affects those living with autism spectrum disorder (ASD) and is associated with significant impairment and treatment recidivism. METHODS We studied the use of accelerated theta burst stimulation (ATBS) for the treatment of refractory MDD in ASD (3 treatments daily x 10 days). This prospective open-label 12-week trial included 10 subjects with a mean age of 21.5 years, randomized to receive unilateral or bilateral stimulation of the dorsolateral prefrontal cortex. RESULTS One participant dropped out of the study due to intolerability. In both treatment arms, depressive symptoms, scored on the Hamilton Depression Rating Scale scores, diminished substantially. At 12 weeks post-treatment, full remission was sustained in 5 subjects and partial remission in 3 subjects. Treatment with ATBS, regardless of the site of stimulation, was associated with a significant, substantial, and sustained improvement in depressive symptomatology via the primary outcome measure, the Hamilton Depression Rating Scale. Additional secondary measures, including self-report depression scales, fluid cognition, and sleep quality, also showed significant improvement. No serious adverse events occurred during the study. Mild transient headaches were infrequently reported, which are expected side effects of ATBS. CONCLUSION Overall, ATBS treatment was highly effective and well-tolerated in individuals with ASD and co-occurring MDD. The findings support the need for a larger, sham-controlled randomized controlled trial to further evaluate efficacy of ATBS in this population.
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Affiliation(s)
- Elizabeth Blank
- Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
| | - Donald L Gilbert
- Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
| | - Steve W Wu
- Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
| | - Travis Larsh
- Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
| | - Rana Elmaghraby
- Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
| | - Rui Liu
- Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
| | - Elizabeth Smith
- Division of Behavioral Medicine and Child Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
| | - Grace Westerkamp
- Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
| | - Yanchen Liu
- Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
| | - Paul S Horn
- Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
| | - Ethan Greenstein
- Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
| | - John A Sweeney
- Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Craig A Erickson
- Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
- Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Ernest V Pedapati
- Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
- Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
- Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
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Bernanke A, Hasley R, Sabetfakhri N, de Wit H, Smith BM, Wang L, Brenner LA, Hanlon C, Philip NS, Ajilore O, Herrold A, Aaronson A. Frontal Pole Neuromodulation for Impulsivity and Suicidality in Veterans With Mild Traumatic Brain Injury and Common Co-Occurring Mental Health Conditions: Protocol for a Pilot Randomized Controlled Trial. JMIR Res Protoc 2024; 13:e58206. [PMID: 39671573 PMCID: PMC11681286 DOI: 10.2196/58206] [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: 03/09/2024] [Revised: 08/13/2024] [Accepted: 09/13/2024] [Indexed: 12/15/2024] Open
Abstract
BACKGROUND Suicide remains a leading cause of death among veterans in the United States, and mild traumatic brain injury (mTBI) increases the risk of suicidal ideation (SI) and suicide attempts (SAs). mTBI worsens impulsivity and contributes to poor social and occupational functioning, which further increases the risk of SI and SAs. Repetitive transcranial magnetic stimulation is a neuromodulatory treatment approach that induces neuroplasticity, potentially repairing neurodamage. Intermittent theta burst stimulation (iTBS) is a second-generation form of transcranial magnetic stimulation that is safe, shorter in duration, displays a minimal side effect profile and is a promising treatment approach for impulsivity in mTBI. Our novel proposed treatment protocol uses frontal pole iTBS to target the ventromedial prefrontal cortex, which may reduce impulsivity by strengthening functional connectivity between the limbic system and frontal cortex, allowing for improved top-down control of impulsive reactions, including SI and SAs. OBJECTIVE The objectives of this study are to (1) develop an iTBS intervention for veterans with mTBI, impulsivity, and SI; (2) assess the feasibility and tolerability of the intervention; and (3) gather preliminary clinical outcome data on SI, impulsivity, and functions that will guide future studies. METHODS This is a pilot, double-blinded, randomized controlled trial. In developing this protocol, we referenced the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. We will enroll 56 participants (28 active iTBS and 28 sham iTBS). The iTBS intervention will be performed daily, 5 days a week, for 2 weeks. We will collect 10 validated, psychometric, quantitative outcome measures before, during, and after the intervention. Measures included will assess functioning, impulsivity, suicidality, posttraumatic stress disorder, and depressive symptoms. We will collect qualitative data through semistructured interviews to elicit feedback on the participants' experiences and symptoms. We will perform quantitative and qualitative analyses to (1) assess the feasibility, tolerability, and acceptability of the treatment; (2) gather advanced neuroimaging data to assess neural changes elicited by treatment; and (3) assess improvements in outcome measures of impulsivity and suicidality in veterans with mTBI. RESULTS This study protocol was approved by the Edward Hines, Jr. VA Hospital Institutional Review Board (Hines IRB number 14-003). This novel treatment is a 5-year research project (April 1, 2023, to March 31, 2028) funded by the Veterans Administration Rehabilitation Research and Development service (CDA2 award IK2 RX002938). Study results will be disseminated at or before the project's end date in March 2028. CONCLUSIONS We will provide preliminary evidence of the safety, feasibility, and acceptability of a novel frontal pole iTBS treatment for mTBI, impulsivity, SI and SAs, and functional deficits. TRIAL REGISTRATION ClinicalTrials.gov NCT05647044; https://clinicaltrials.gov/study/NCT05647044. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) PRR1-10.2196/58206.
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Affiliation(s)
- Alyssa Bernanke
- Northwestern University Feinberg School of Medicine, Chicago, IL, United States
| | - Rebecca Hasley
- Edward Hines Department of Veteran Affairs, Mental Health Service Line, Hines, IL, United States
| | | | | | - Bridget M Smith
- SCI/D National Program Office, Veterans Health Administration, Washington, DC, United States
| | - Lei Wang
- The Ohio State University, Columbus, OH, United States
| | - Lisa A Brenner
- University of Colorado, Anschutz Medical Campus, Aurora, CO, United States
| | | | - Noah S Philip
- Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System, Providence, RI, United States
| | | | - Amy Herrold
- Edward Hines Department of Veteran Affairs, Mental Health Service Line, Hines, IL, United States
| | - Alexandra Aaronson
- Edward Hines Department of Veteran Affairs, Mental Health Service Line, Hines, IL, United States
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Qiu J, Xu J, Cai Y, Li M, Peng Y, Xu Y, Chen G. Catgut embedding in acupoints combined with repetitive transcranial magnetic stimulation for the treatment of postmenopausal osteoporosis: study protocol for a randomized clinical trial. Front Neurol 2024; 15:1295429. [PMID: 38606276 PMCID: PMC11008468 DOI: 10.3389/fneur.2024.1295429] [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: 09/16/2023] [Accepted: 03/11/2024] [Indexed: 04/13/2024] Open
Abstract
Background To date, the clinical modulation for bone metabolism based on the neuro-bone mass regulation theory is still not popular. The stimulation of nerve systems to explore novel treatments for Postmenopausal osteoporosis (PMOP) is urgent and significant. Preliminary research results suggested that changes brain function and structure may play a crucial role in bone metabolism with PMOP. Thus, we set up a clinical trial to investigate the effect of the combination of repetitive transcranial magnetic stimulation (rTMS) and catgut embedding in acupoints (CEA) for PMOP and to elucidate the central mechanism of this neural stimulation in regulating bone metabolism. Method This trial is a prospective and randomized controlled trial. 96 PMOP participants will be randomized in a 1:1:1 ratio into a CEA group, an rTMS group, or a combined one. Participants will receive CEA, rTMS, or combined therapy for 3 months with 8 weeks of follow-up. The primary outcomes will be the changes in Bone Mineral Density scores, total efficiency of Chinese Medicine Symptoms before and after treatment. Secondary outcomes include the McGill Pain Questionnaire Short-Form, Osteoporosis Symptom Score, Mini-Mental State Examination, and Beck Depression Inventory-II. The leptin, leptin receptor, and norepinephrine levels of peripheral blood must be measured before and after treatment. Adverse events that occur during the trial will be recorded. Discussion CEA achieves brain-bone mass regulation through the bottom-up way of peripheral-central while rTMS achieves it through the top-down stimulation of central-peripheral. CEA combined with rTMS can stimulate the peripheral-central at the same time and promote peripheral bone mass formation. The combination of CEA and rTMS may play a coordinating, synergistic, and side-effect-reducing role, which is of great clinical significance in exploring better treatment options for PMOP.Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2300073863.
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Affiliation(s)
- Jingjing Qiu
- Shenzhen Bao'an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - JiaZi Xu
- Clinical Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yingyue Cai
- Clinical Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Minghong Li
- Clinical Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yingsin Peng
- Shenzhen Bao'an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Yunxiang Xu
- Clinical Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Guizhen Chen
- Shenzhen Bao'an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
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Dębowska W, Więdłocha M, Dębowska M, Kownacka Z, Marcinowicz P, Szulc A. Transcranial magnetic stimulation and ketamine: implications for combined treatment in depression. Front Neurosci 2023; 17:1267647. [PMID: 37954877 PMCID: PMC10637948 DOI: 10.3389/fnins.2023.1267647] [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: 07/27/2023] [Accepted: 10/09/2023] [Indexed: 11/14/2023] Open
Abstract
Drug-resistant mental disorders, particularly treatment-resistant depression, pose a significant medical and social problem. To address this challenge, modern psychiatry is constantly exploring the use of novel treatment methods, including biological treatments, such as transcranial magnetic stimulation (TMS), and novel rapid-acting antidepressants, such as ketamine. While both TMS and ketamine demonstrate high effectiveness in reducing the severity of depressive symptoms, some patients still do not achieve the desired improvement. Recent literature suggests that combining these two methods may yield even stronger and longer-lasting results. This review aims to consolidate knowledge in this area and elucidate the potential mechanisms of action underlying the increased efficacy of combined treatment, which would provide a foundation for the development and optimization of future treatment protocols.
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Affiliation(s)
- Weronika Dębowska
- Department of Psychiatry, Faculty of Health Sciences, Medical University of Warsaw, Warsaw, Poland
| | - Magdalena Więdłocha
- Department of Psychiatry, Faculty of Health Sciences, Medical University of Warsaw, Warsaw, Poland
- KeyClinic, Warsaw, Poland
| | - Marta Dębowska
- Department of Psychiatry, Faculty of Health Sciences, Medical University of Warsaw, Warsaw, Poland
| | - Zuzanna Kownacka
- Department of Psychiatry, Faculty of Health Sciences, Medical University of Warsaw, Warsaw, Poland
| | - Piotr Marcinowicz
- Department of Psychiatry, Faculty of Health Sciences, Medical University of Warsaw, Warsaw, Poland
- KeyClinic, Warsaw, Poland
| | - Agata Szulc
- Department of Psychiatry, Faculty of Health Sciences, Medical University of Warsaw, Warsaw, Poland
- MindHealth, Warsaw, Poland
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Ross RE, VanDerwerker CJ, George MS, Gregory CM. Feasibility of performing a multi-arm clinical trial examining the novel combination of repetitive transcranial magnetic stimulation and aerobic exercise for post-stroke depression. Top Stroke Rehabil 2023; 30:649-662. [PMID: 36606675 PMCID: PMC10323040 DOI: 10.1080/10749357.2023.2165258] [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: 06/24/2022] [Accepted: 01/02/2023] [Indexed: 01/07/2023]
Abstract
BACKGROUND Post-stroke depression (PSD) occurs in approximately one-third of chronic stroke survivors. Although pharmacotherapy reduces depressive symptoms, side effects are common and stroke survivors have increased likelihood of multimorbidity and subsequent polypharmacy. Thus, alternative non-pharmacological treatments are needed. Combining two non-pharmacological anti-depressant treatments, aerobic exercise (AEx) and repetitive transcranial magnetic stimulation (rTMS), has been demonstrated to be feasible and well-tolerated in chronic stroke survivors. OBJECTIVES The purpose of this trial was to determine the feasibility of conducting a multi-arm combinatorial trial of rTMS and AEx and to provide an estimate of effect size of rTMS+AEx on PSD symptoms. METHODS Twenty-four participants were allocated to one of four treatment arms AEx, rTMS, rTMS+AEx, or non-depressed Control receiving AEx. All participants received a total of 24 treatment sessions. Participant adherence was the primary outcome measure for feasibility and within group effect sizes in Patient Health Questionnaire-9 (PHQ-9) score was the primary outcome for preliminary efficacy. RESULTS Mean adherence rates to the exercise intervention for AEx, rTMS+AEx, and Control subjects were 83%, 98%, and 95%, respectively. Mean adherence rates for rTMS and rTMS+AEx subjects were 97% and 99%, respectively. The rTMS and rTMS+AEx treatment groups demonstrated clinically significant reductions of 10.5 and 6.2 points in PHQ-9 scores, respectively. CONCLUSION Performing a multi-arm combinatorial trial examining the effect of rTMS+AEx on PSD appears feasible. All treatment arms demonstrated strong adherence to their respective interventions and were well received. rTMS and the combination of AEx with rTMS may be alternative treatments for PSD.
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Affiliation(s)
- Ryan E. Ross
- Ralph H. Johnson Veterans Affairs Health Care System, Charleston, SC
- Department of Health Sciences and Research, Medical University of South Carolina, Charleston, SC
| | | | - Mark S. George
- Ralph H. Johnson Veterans Affairs Health Care System, Charleston, SC
- Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC
| | - Chris M. Gregory
- Ralph H. Johnson Veterans Affairs Health Care System, Charleston, SC
- Department of Health Sciences and Research, Medical University of South Carolina, Charleston, SC
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Alaghband-rad J, Motamed M, Khazaeipour Z, Farhadbeigi P. Pattern of Compliance and Efficacy of Repetitive Transcranial Magnetic Stimulation Protocol for Treating Major Depressive Disorder Among Treatment Participants and Completers: A Report From Iran. Basic Clin Neurosci 2023; 14:511-518. [PMID: 38050571 PMCID: PMC10693813 DOI: 10.32598/bcn.2021.3369.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 06/07/2021] [Accepted: 07/10/2021] [Indexed: 12/06/2023] Open
Abstract
Introduction Since the introduction of the Food and Drug Administration (FDA)-approved repetitive transcranial magnetic stimulation (rTMS) intervention in 2008, a breakthrough has been made in treating major depressive disorder (MDD). However, many sessions of treatment and its cost make it inconvenient for those who seek treatment, especially in large cities as well as in developing countries. Methods A total of 22 patients (out of initial 24 referrals) who met diagnostic and statistical manual of mental disorders, 4th edition (DSM IV) criteria for MDD were enrolled in the study. All subjects had to fail at least one prior treatment for depression. The patients received the FDA-approved protocol of high-frequency (10 Hz) rTMS over the left dorsolateral prefrontal cortex. Results Seventeen out of twenty-two cases showed significant improvements after two weeks of treatment. Only six patients continued their treatments for the next two to four weeks. Conclusion We have replicated other studies showing that the use of rTMS is effective for many patients with MDD without major side effects and their improvements are measurable mostly after two weeks. Our data highlight the importance of the application of more convenient protocols that require fewer sessions on fewer days to help with compliance and outcome, particularly in large populated cities and countries, such as Iran going through economic hardship. Highlights Repetitive transcranial magnetic stimulation (rTMS) is effective for treating major depresion.Improvemens are measurable after 2 weeks of treating with rTMS.Compliance is a major factorto for completing rTMS protocols. Plain Language Summary Major depression is one of the most common psychiatric disorders leading to debilitating course causing significant burden for the society. Many cases with major depression are resistent to treatment as they try multiple interventions with no success. This condition is also called refractory depression. rTMS is a novel intervention introduced first almost two decades ago to treat refractory depression among some other psychiatric disorders. In this intervention pulses generated by magnetic stimulation over the brain leads to improvement is depression. As this treatment is safe with no pain and discomfort there have been much interest in the field to use it more frequently. rTMS is usually done over 15-30 sessions with its maximum effects appearing within the first two weeks of treatment. The number of sessions is a potential factor contributing to poor compliance in some cases especially those living in large metropolitan areas. In this paper we explored compliance and effect of treatment within the first two weeks among a group of patients in a private outpatient clinic of a large metropolitan area.
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Affiliation(s)
- Javad Alaghband-rad
- Department of Psychiatry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahtab Motamed
- Department of Psychiatry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Khazaeipour
- Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Parvaneh Farhadbeigi
- Academic Center for Education, Culture and Research, Alborz Branches, Karaj, Iran
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Asp AJ, Chintaluru Y, Hillan S, Lujan JL. Targeted neuroplasticity in spatiotemporally patterned invasive neuromodulation therapies for improving clinical outcomes. Front Neuroinform 2023; 17:1150157. [PMID: 37035718 PMCID: PMC10080034 DOI: 10.3389/fninf.2023.1150157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 03/06/2023] [Indexed: 04/11/2023] Open
Affiliation(s)
- Anders J. Asp
- Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN, United States
| | - Yaswanth Chintaluru
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, United States
- Department of Neurology and Neurosurgery, University of Colorado Anschutz School of Medicine, Aurora, CO, United States
| | - Sydney Hillan
- Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN, United States
| | - J. Luis Lujan
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, United States
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, United States
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Staat C, Gattinger N, Gleich B. PLUSPULS: A transcranial magnetic stimulator with extended pulse protocols. HARDWAREX 2023; 13:e00380. [PMID: 36578972 PMCID: PMC9791927 DOI: 10.1016/j.ohx.2022.e00380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
Transcranial magnetic stimulation (TMS) is increasingly applied in basic neuroscience while its field of usage for diagnosing and treating various neurological diseases broadens steadily. A TMS device generates a current pulse in the reach of several thousand ampére to produce a magnetic pulse which induces an electric field around neurons. This electric field, if high enough to depolarize the neuron membrane, generates an action potential at the neuron which travels down the neurons connected to it. The PLUSPULS TMS generates this magnetic pulse by pre-charging a pulse capacitor C with the voltage V C 0 and connecting it with a stimulation coil L . The oscillation of the resonance circuit is cut off after one period and is called a biphasic pulse. PLUSPULS is a high frequency stimulator with inter stimulus intervals (ISI) down to 1ms which enables different pulse protocols as paired pulse or quadri theta burst stimulation. A GUI on PC allows a flexible control of PLUSPULS with varying amplitudes and ISI in one burst. The modular hardware and the control via GUI on PC allows for an easier adjustment on requirements to come. The article provides design considerations, hardware, firmware and software to reconstruct a modular biphasic TMS with enhanced charging network to enable extended pulse protocols.
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Li G, Lei L, Yang C, Liu Z, Zhang KR. Add-On Intermittent Theta Burst Stimulation Improves the Efficacy of First-Episode and Recurrent Major Depressive Disorder: Real-World Clinical Practice. Neuropsychiatr Dis Treat 2023; 19:109-116. [PMID: 36660319 PMCID: PMC9844137 DOI: 10.2147/ndt.s388774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 12/06/2022] [Indexed: 01/15/2023] Open
Abstract
OBJECTIVE Repetitive transcranial magnetic stimulation (rTMS) is an effective and evidence-based treatment for major depressive disorder (MDD). This retrospective study aimed to explore the efficacy of add-on iTBS treatment in MDD in real-world clinical practice. METHODS One hundred and fifty-nine inpatients with MDD in a general hospital were included in this study. These patients were treated with at least 8 sessions of iTBS, in addition to antidepressants and supportive psychotherapy. Symptoms of depression and anxiety were assessed with the Hamilton Depression Rating Scale (HDRS) and the Hamilton Rating Scale for Anxiety (HAMA) at baseline and after 2-4 weeks of treatment. The improvement degree of depressive and anxious symptoms was compared between the first-episode MDD (n=107) and recurrent MDD (n=52) groups. RESULTS Depressive and anxious symptoms were reduced significantly after the add-on iTBS treatment; the response and remission rates in the first-episode MDD group were 55.14% and 28.97%, which were 63.46% and 28.85% for the recurrent MDD group, respectively (P>0.05). The response rate and remission rate of anxiety in the first-episode MDD group was 64.13% and 57.45% for HAMA, and 66.67% and 62.50% for the recurrent MDD group (P>0.05). CONCLUSION Our findings indicated that antidepressant and anti-anxiety efficacy of add-on iTBS treatment remains equivocal in real-world clinical practice, regardless of a first-episode depression diagnosis or recurrent depression.
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Affiliation(s)
- Gaizhi Li
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, People's Republic of China.,Department of Psychiatry, First Clinical Medical College, Shanxi Medical University, Taiyuan, People's Republic of China
| | - Lei Lei
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, People's Republic of China
| | - Chunxia Yang
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, People's Republic of China
| | - Zhifen Liu
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, People's Republic of China
| | - Ke-Rang Zhang
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, People's Republic of China.,Department of Psychiatry, First Clinical Medical College, Shanxi Medical University, Taiyuan, People's Republic of China
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Wang W, Zhu Y, Wang L, Mu L, Zhu L, Ding D, Ren Z, Yang D, Tang H, Zhang L, Song P, Wei H, Chang L, Wang Z, Ling Q, Gao H, Liu L, Jiao D, Xu H. High-frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex reduces drug craving and improves decision-making ability in methamphetamine use disorder. Psychiatry Res 2022; 317:114904. [PMID: 36265196 DOI: 10.1016/j.psychres.2022.114904] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 10/09/2022] [Accepted: 10/10/2022] [Indexed: 01/05/2023]
Abstract
Methamphetamine abuse is escalating worldwide. Its strong and irreversible neurotoxicity generally causes structural and functional changes in the brain. Repetitive transcranial magnetic stimulation (rTMS) as a non-invasive tool can be used to modulate neuronal activity, cortical excitability, and dopaminergic neurotransmission. This study aims to explore the efficacy of high-frequency rTMS in reducing drug craving and increasing decision-making ability for methamphetamine use disorder patients. Sixty-four methamphetamine use disorder patients were randomized to sham rTMS group and 10-Hz rTMS group. Visual analog scale (VAS) and Iowa game test (IGT) were used to evaluate drug craving and cognitive decision-making ability before and after treatment. Before the treatment, the two groups had no differences in the scores of VAS and IGT. After the intervention, VAS scores of 10-Hz rTMS group were significantly lower than that of sham rTMS group. In addition, the two groups had significant differences in the net score of IGT on block 4 and block 5, which favoured the 10-Hz rTMS group. Taken together, the present results suggest that High-frequency rTMS can be used to reduce drug craving and improve decision-making function for methamphetamine use disorder.
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Affiliation(s)
- Wenjuan Wang
- School of Mental Health, Bengbu Medical College, Bengbu, Anhui 233030, China
| | - Yuqiong Zhu
- School of Mental Health, Bengbu Medical College, Bengbu, Anhui 233030, China
| | - Lijin Wang
- School of Mental Health, Bengbu Medical College, Bengbu, Anhui 233030, China
| | - LinLin Mu
- School of Mental Health, Bengbu Medical College, Bengbu, Anhui 233030, China
| | - Lin Zhu
- School of Mental Health, Bengbu Medical College, Bengbu, Anhui 233030, China
| | - Dongyan Ding
- School of Mental Health, Bengbu Medical College, Bengbu, Anhui 233030, China
| | - Zixuan Ren
- School of Mental Health, Bengbu Medical College, Bengbu, Anhui 233030, China
| | - Dengxian Yang
- School of Mental Health, Bengbu Medical College, Bengbu, Anhui 233030, China
| | - Huajun Tang
- Compulsory Isolated Drug Rehabilitation Center, Bengbu, Anhui 233030, China
| | - Lei Zhang
- School of Mental Health, Bengbu Medical College, Bengbu, Anhui 233030, China
| | - Peipei Song
- School of Mental Health, Bengbu Medical College, Bengbu, Anhui 233030, China
| | - Huafeng Wei
- School of Mental Health, Bengbu Medical College, Bengbu, Anhui 233030, China
| | - Leixin Chang
- School of Mental Health, Bengbu Medical College, Bengbu, Anhui 233030, China
| | - Zixu Wang
- School of Mental Health, Bengbu Medical College, Bengbu, Anhui 233030, China
| | - Qiang Ling
- Compulsory Isolated Drug Rehabilitation Center, Bengbu, Anhui 233030, China
| | - He Gao
- Compulsory Isolated Drug Rehabilitation Center, Bengbu, Anhui 233030, China
| | - Luying Liu
- School of Mental Health, Bengbu Medical College, Bengbu, Anhui 233030, China
| | - Dongliang Jiao
- School of Mental Health, Bengbu Medical College, Bengbu, Anhui 233030, China.
| | - Huashan Xu
- School of Mental Health, Bengbu Medical College, Bengbu, Anhui 233030, China.
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Larsen NY, Vihrs N, Møller J, Sporring J, Tan X, Li X, Ji G, Rajkowska G, Sun F, Nyengaard JR. Layer III pyramidal cells in the prefrontal cortex reveal morphological changes in subjects with depression, schizophrenia, and suicide. Transl Psychiatry 2022; 12:363. [PMID: 36064829 PMCID: PMC9445178 DOI: 10.1038/s41398-022-02128-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 08/15/2022] [Accepted: 08/18/2022] [Indexed: 11/09/2022] Open
Abstract
Brodmann Area 46 (BA46) has long been regarded as a hotspot of disease pathology in individuals with schizophrenia (SCH) and major depressive disorder (MDD). Pyramidal neurons in layer III of the Brodmann Area 46 (BA46) project to other cortical regions and play a fundamental role in corticocortical and thalamocortical circuits. The AutoCUTS-LM pipeline was used to study the 3-dimensional structural morphology and spatial organization of pyramidal cells. Using quantitative light microscopy, we used stereology to calculate the entire volume of layer III in BA46 and the total number and density of pyramidal cells. Volume tensors estimated by the planar rotator quantified the volume, shape, and nucleus displacement of pyramidal cells. All of these assessments were carried out in four groups of subjects: controls (C, n = 10), SCH (n = 10), MDD (n = 8), and suicide subjects with a history of depression (SU, n = 11). SCH subjects had a significantly lower somal volume, total number, and density of pyramidal neurons when compared to C and tended to show a volume reduction in layer III of BA46. When comparing MDD subjects with C, the measured parameters were inclined to follow SCH, although there was only a significant reduction in pyramidal total cell number. While no morphometric differences were observed between SU and MDD, SU had a significantly higher total number of pyramidal cells and nucleus displacement than SCH. Finally, no differences in the spatial organization of pyramidal cells were found among groups. These results suggest that despite significant morphological alterations in layer III of BA46, which may impair prefrontal connections in people with SCH and MDD, the spatial organization of pyramidal cells remains the same across the four groups and suggests no defects in neuronal migration. The increased understanding of pyramidal cell biology may provide the cellular basis for symptoms and neuroimaging observations in SCH and MDD patients.
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Affiliation(s)
- Nick Y. Larsen
- grid.7048.b0000 0001 1956 2722Core Centre for Molecular Morphology, Section for Stereology and Microscopy, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark ,grid.7048.b0000 0001 1956 2722Center of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark ,Sino-Danish Center for Education and Research, Aarhus, Denmark ,grid.410726.60000 0004 1797 8419University of the Chinese Academy of Sciences, Beijing, China ,grid.5117.20000 0001 0742 471XCentre for Stochastic Geometry and Advanced Bioimaging, Aalborg University, Aarhus University and University of Copenhagen, Aarhus, Denmark
| | - Ninna Vihrs
- grid.5117.20000 0001 0742 471XDepartment of Mathematical Sciences, Aalborg University, Aalborg, Denmark
| | - Jesper Møller
- grid.5117.20000 0001 0742 471XCentre for Stochastic Geometry and Advanced Bioimaging, Aalborg University, Aarhus University and University of Copenhagen, Aarhus, Denmark ,grid.5117.20000 0001 0742 471XDepartment of Mathematical Sciences, Aalborg University, Aalborg, Denmark
| | - Jon Sporring
- grid.5117.20000 0001 0742 471XCentre for Stochastic Geometry and Advanced Bioimaging, Aalborg University, Aarhus University and University of Copenhagen, Aarhus, Denmark ,grid.5254.60000 0001 0674 042XDepartment of Computer Science, University of Copenhagen, Copenhagen, Denmark
| | - Xueke Tan
- grid.418856.60000 0004 1792 5640National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China ,grid.418856.60000 0004 1792 5640Center for Biological Imaging, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
| | - Xixia Li
- grid.5254.60000 0001 0674 042XDepartment of Computer Science, University of Copenhagen, Copenhagen, Denmark ,grid.418856.60000 0004 1792 5640National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
| | - Gang Ji
- grid.5254.60000 0001 0674 042XDepartment of Computer Science, University of Copenhagen, Copenhagen, Denmark ,grid.418856.60000 0004 1792 5640National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
| | - Grazyna Rajkowska
- grid.410721.10000 0004 1937 0407Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS USA
| | - Fei Sun
- Sino-Danish Center for Education and Research, Aarhus, Denmark ,grid.410726.60000 0004 1797 8419University of the Chinese Academy of Sciences, Beijing, China ,grid.418856.60000 0004 1792 5640National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China ,grid.418856.60000 0004 1792 5640Center for Biological Imaging, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
| | - Jens R. Nyengaard
- grid.7048.b0000 0001 1956 2722Core Centre for Molecular Morphology, Section for Stereology and Microscopy, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark ,Sino-Danish Center for Education and Research, Aarhus, Denmark ,grid.5117.20000 0001 0742 471XCentre for Stochastic Geometry and Advanced Bioimaging, Aalborg University, Aarhus University and University of Copenhagen, Aarhus, Denmark ,grid.154185.c0000 0004 0512 597XDepartment of Pathology, Aarhus University Hospital, Aarhus, Denmark
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12
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Fang F, Godlewska B, Cho RY, Savitz SI, Selvaraj S, Zhang Y. Personalizing repetitive transcranial magnetic stimulation for precision depression treatment based on functional brain network controllability and optimal control analysis. Neuroimage 2022; 260:119465. [PMID: 35835338 DOI: 10.1016/j.neuroimage.2022.119465] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 06/05/2022] [Accepted: 07/11/2022] [Indexed: 11/16/2022] Open
Abstract
Brain neuromodulation effectively treats neurological diseases and psychiatric disorders such as Depression. However, due to patient heterogeneity, neuromodulation treatment outcomes are often highly variable, requiring patient-specific stimulation protocols throughout the recovery stages to optimize treatment outcomes. Therefore, it is critical to personalize neuromodulation protocol to optimize the patient-specific stimulation targets and parameters by accommodating inherent interpatient variability and intersession alteration during treatments. The study aims to develop a personalized repetitive transcranial magnetic stimulation (rTMS) protocol and evaluate its feasibility in optimizing the treatment efficiency using an existing dataset from an antidepressant experimental imaging study in depression. The personalization of the rTMS treatment protocol was achieved by personalizing both stimulation targets and parameters via a novel approach integrating the functional brain network controllability analysis and optimal control analysis. First, the functional brain network controllability analysis was performed to identify the optimal rTMS stimulation target from the effective connectivity network constructed from patient-specific resting-state functional magnetic resonance imaging data. The optimal control algorithm was then applied to optimize the rTMS stimulation parameters based on the optimized target. The performance of the proposed personalized rTMS technique was evaluated using datasets collected from a longitudinal antidepressant experimental imaging study in depression (n = 20). Simulation models demonstrated that the proposed personalized rTMS protocol outperformed the standard rTMS treatment by efficiently steering a depressive resting brain state to a healthy resting brain state, indicated by the significantly less control energy needed and higher model fitting accuracy achieved. The node with the maximum average controllability of each patient was designated as the optimal target region for the personalized rTMS protocol. Our results also demonstrated the theoretical feasibility of achieving comparable neuromodulation efficacy by stimulating a single node compared to stimulating multiple driver nodes. The findings support the feasibility of developing personalized neuromodulation protocols to more efficiently treat depression and other neurological diseases.
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Affiliation(s)
- Feng Fang
- Department of Biomedical Engineering, University of Houston, Houston, TX, USA
| | - Beata Godlewska
- Department of Psychiatry, Medical Sciences Division, University of Oxford, United Kingdom; Oxford Health NHS Foundation Trust, Oxford, United Kingdom
| | - Raymond Y Cho
- Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, and Menninger Clinic, Houston, TX, United States
| | - Sean I Savitz
- Department of Neurology, The McGovern Medical School of UT Health Houston, Houston, TX, United States
| | - Sudhakar Selvaraj
- Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, The McGovern Medical School of UT Health Houston, Houston, TX, United States
| | - Yingchun Zhang
- Department of Biomedical Engineering, University of Houston, Houston, TX, USA.
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13
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Xu Y, Peremans K, Courtyn J, Audenaert K, Dobbeleir A, D'Asseler Y, Achten E, Saunders J, Baeken C. The Impact of Accelerated HF-rTMS on Canine Brain Metabolism: An [18F]-FDG PET Study in Healthy Beagles. Front Vet Sci 2022; 9:800158. [PMID: 35280129 PMCID: PMC8907524 DOI: 10.3389/fvets.2022.800158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 01/26/2022] [Indexed: 12/04/2022] Open
Abstract
Background Repetitive transcranial magnetic stimulation (rTMS) has been proven to be a useful tool for the treatment of several severe neuropsychiatric disorders. Accelerated (a)rTMS protocols may have the potential to result in faster clinical improvements, but the effects of such accelerated paradigms on brain function remain to be elucidated. Objectives This sham-controlled arTMS study aimed to evaluate the immediate and delayed effects of accelerated high frequency rTMS (aHF-rTMS) on glucose metabolism in healthy beagle dogs when applied over the left frontal cortex. Methods Twenty-four dogs were randomly divided into four unequal groups: five active (n = 8)/ sham (n = 4) stimulation sessions (five sessions in 1 day), 20 active (n = 8)/ sham (n = 4) stimulation sessions (five sessions/ day for 4 days), respectively. [18F] FDG PET scans were obtained at baseline, 24 h poststimulation, after 1 and 3 months post the last stimulation session. We explicitly focused on four predefined regions of interest (left/right prefrontal cortex and left/right hippocampus). Results One day of active aHF-rTMS- and not sham- significantly increased glucose metabolism 24 h post-active stimulation in the left frontal cortex only. Four days of active aHF-rTMS only resulted in a nearly significant metabolic decrease in the left hippocampus after 1 month. Conclusions Like in human psychiatric disorders, active aHF-rTMS in healthy beagles modifies glucose metabolism, although differently immediately or after 1 month post stimulation. aHF-rTMS may be also a valid option to treat mentally disordered dogs.
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Affiliation(s)
- Yangfeng Xu
- Ghent Experimental Psychiatry (GHEP) Laboratory, Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
- Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
- *Correspondence: Yangfeng Xu
| | - Kathelijne Peremans
- Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Jan Courtyn
- Department of Radiology and Nuclear Medicine, Medical Molecular Imaging and Therapy, Ghent University Hospital, Ghent, Belgium
| | - Kurt Audenaert
- Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University Hospital, Ghent University, Ghent, Belgium
| | - Andre Dobbeleir
- Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Yves D'Asseler
- Department of Radiology and Nuclear Medicine, Medical Molecular Imaging and Therapy, Ghent University Hospital, Ghent, Belgium
| | - Eric Achten
- Department of Radiology and Nuclear Medicine, Medical Molecular Imaging and Therapy, Ghent University Hospital, Ghent, Belgium
| | - Jimmy Saunders
- Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Chris Baeken
- Ghent Experimental Psychiatry (GHEP) Laboratory, Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
- Department of Psychiatry, Faculty of Medicine and Pharmacy, Vrije University Brussels, Brussels, Belgium
- Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands
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14
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Kawabata Y, Imazu SI, Matsumoto K, Toyoda K, Kawano M, Kubo Y, Kinoshita S, Nishizawa Y, Kanazawa T. rTMS Therapy Reduces Hypofrontality in Patients With Depression as Measured by fNIRS. Front Psychiatry 2022; 13:814611. [PMID: 35815029 PMCID: PMC9257165 DOI: 10.3389/fpsyt.2022.814611] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Accepted: 05/26/2022] [Indexed: 11/15/2022] Open
Abstract
Multichannel functional near-infrared spectroscopy (fNIRS) is a tool used to capture changes in cerebral blood flow. A consistent result for depression is a decrease in blood flow in the frontal cortex leading to hypofrontality, which indicates multidomain functional impairment. Repetitive transcranial magnetic stimulation (rTMS) and elective convulsive therapy (ECT) are alternatives to antidepressant drugs for the treatment of depression but the underlying mechanism is yet to be elucidated. The aim of the current study was to evaluate cerebral blood flow using fNIRS following rTMS treatment in patients with depression. The cerebral blood flow of 15 patients with moderate depression after rTMS treatment was measured using fNIRS. While there was clear hypofrontality during pre-treatment (5 ± 2.5), a notable increase in oxygenated hemoglobin was observed after 30 sessions with rTMS (50 ± 15). This increased blood flow was observed in a wide range of channels in the frontal cortex; however, the centroid values were similar between the treatments. Increased blood flow leads to the activation of neuronal synapses, as noted with other neuromodulation treatments such as electroconvulsive therapy. This study describes the rTMS-induced modulation of blood oxygenation response over the prefrontal cortex in patients with depression, as captured by fNIRS. Future longitudinal studies are needed to assess cerebral blood flow dynamics during rTMS treatment for depression.
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Affiliation(s)
- Yasuo Kawabata
- Department of Neuropsychiatry, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Shin-Ichi Imazu
- Department of Neuropsychiatry, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Koichi Matsumoto
- Department of Neuropsychiatry, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Katsunori Toyoda
- Department of Neuropsychiatry, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Makoto Kawano
- Department of Neuropsychiatry, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Yoichiro Kubo
- Department of Neuropsychiatry, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Shinya Kinoshita
- Department of Neuropsychiatry, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Yoshitaka Nishizawa
- Department of Neuropsychiatry, Osaka Medical and Pharmaceutical University, Osaka, Japan.,Stanford University, Stanford, CA, United States
| | - Tetsufumi Kanazawa
- Department of Neuropsychiatry, Osaka Medical and Pharmaceutical University, Osaka, Japan.,The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia
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15
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Tasleem M, Alrehaily A, Almeleebia TM, Alshahrani MY, Ahmad I, Asiri M, Alabdallah NM, Saeed M. Investigation of Antidepressant Properties of Yohimbine by Employing Structure-Based Computational Assessments. Curr Issues Mol Biol 2021; 43:1805-1827. [PMID: 34889886 PMCID: PMC8929124 DOI: 10.3390/cimb43030127] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 10/14/2021] [Accepted: 10/18/2021] [Indexed: 12/26/2022] Open
Abstract
The use of pharmaceuticals to treat Major Depressive Disorder (MDD) has several drawbacks, including severe side effects. Natural compounds with great efficacy and few side effects are in high demand due to the global rise in MDD and ineffective treatment. Yohimbine, a natural compound, has been used to treat various ailments, including neurological conditions, since ancient times. Serotonergic neurotransmission plays a crucial role in the pathogenesis of depression; thus, serotonergic receptor agonist/antagonistic drugs are promising anti-depressants. Yohimbine was investigated in this study to determine its antidepressant activity using molecular docking and pharmacokinetic analyses. Additionally, the in silico mutational study was carried out to understand the increase in therapeutic efficiency using site-directed mutagenesis. Conformational changes and fluctuations occurring during wild type and mutant serotonergic receptor, 5-hydroxytryptamine receptors 1A (5HT1A) and yohimbine were assessed by molecular dynamics MD simulation studies. Yohimbine was found to satisfy all the parameters for drug-likeness and pharmacokinetics analysis. It was found to possess a good dock score and hydrogen-bond interactions with wild type 5HT1A structure. Our findings elaborate the substantial efficacy of yohimbine against MDD; however, further bench work studies may be carried out to prove the same.
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Affiliation(s)
- Munazzah Tasleem
- School of Electronic Science and Engineering, University of Electronic Science and Technology of China, Chengdu 610054, China
- Correspondence: (M.T.); (M.S.)
| | - Abdulwahed Alrehaily
- Department of Biology, Faculty of Science, Islamic University of Madinah, P.O. Box 170, Madinah 42351, Saudi Arabia;
| | - Tahani M. Almeleebia
- Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, P.O. Box 61413, Abha 62529, Saudi Arabia;
| | - Mohammad Y. Alshahrani
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, P.O. Box 61413, Abha 62529, Saudi Arabia; (M.Y.A.); (I.A.); (M.A.)
| | - Irfan Ahmad
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, P.O. Box 61413, Abha 62529, Saudi Arabia; (M.Y.A.); (I.A.); (M.A.)
| | - Mohammed Asiri
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, P.O. Box 61413, Abha 62529, Saudi Arabia; (M.Y.A.); (I.A.); (M.A.)
| | - Nadiyah M. Alabdallah
- Department of Biology, College of Science, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia;
| | - Mohd Saeed
- Department of Biology, College of Sciences University of Hail, P.O. Box 2440, Hail 2440, Saudi Arabia
- Correspondence: (M.T.); (M.S.)
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16
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Tumova MA, Muslimova LM, Stanovaya VV, Abdyrakhmanova AK, Ivanov MV. [Contemporary methods of non-drug therapy for depression]. Zh Nevrol Psikhiatr Im S S Korsakova 2021; 121:91-98. [PMID: 34405663 DOI: 10.17116/jnevro202112105291] [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] [Indexed: 11/17/2022]
Abstract
The review presents information on the most effective current non-drug methods of treatment of depression used in practice. A review of publications in PubMed and PsycINFO and Cochrane Library over the past 10 years was conducted. Non-drug biological therapies demonstrate high efficacy in the reduction of depressive symptoms in patients with recurrent depressive disorder. The use of non-drug therapy does not preclude the continuation of pharmacological therapy. In order to choose an optimal method of treatment, the psychophysical state of a patient, severity of depressive symptoms, response to drug therapy, and possibility of prescribing pharmacological therapy should be taken into account, and the principles of evidence-based medicine should be taken into consideration when making a decision.
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Affiliation(s)
- M A Tumova
- Bekhterev National Research Medical Centre for Psychiatry and Neurology, St. Petersburg, Russia
| | - L M Muslimova
- Bekhterev National Research Medical Centre for Psychiatry and Neurology, St. Petersburg, Russia
| | - V V Stanovaya
- Bekhterev National Research Medical Centre for Psychiatry and Neurology, St. Petersburg, Russia
| | - A K Abdyrakhmanova
- Bekhterev National Research Medical Centre for Psychiatry and Neurology, St. Petersburg, Russia
| | - M V Ivanov
- Bekhterev National Research Medical Centre for Psychiatry and Neurology, St. Petersburg, Russia
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17
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Miuli A, Sepede G, Stigliano G, Mosca A, Di Carlo F, d’Andrea G, Lalli A, Spano MC, Pettorruso M, Martinotti G, di Giannantonio M. Hypomanic/manic switch after transcranial magnetic stimulation in mood disorders: A systematic review and meta-analysis. World J Psychiatry 2021; 11:477-490. [PMID: 34513609 PMCID: PMC8394688 DOI: 10.5498/wjp.v11.i8.477] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 03/24/2021] [Accepted: 07/20/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Nowadays there is an increasing use of transcranial magnetic stimulation (TMS) both in neurological and psychiatric fields. After Food and Drug Administration approval of TMS for the therapy of treatment-resistant depression, TMS has been widely used in the context of mood disorders (MD). However, growing reports regarding the possibility of developing hypomanic/manic switch (HMS) have generated concern regarding its use in MDs.
AIM To investigate the actual risk of developing HMS due to TMS in the treatment of MD.
METHODS We led our research on PubMed, Scopus and Web of Science on March 22, 2020, in accordance to the PRISMA guidelines for systematic review. Only double blind/single blind studies, written in English and focused on the TMS treatment of MD, were included. A meta-analysis of repetitive TMS protocol studies including HMS was conducted using RevMan 5.4 software. The assessment of Risk of Bias was done using Cochrane risk of bias tool. This protocol was registered on PROSPERO with the CRD42020175811 code.
RESULTS Twenty-five studies were included in our meta-analysis: Twenty-one double blind randomized controlled trials (RCT) and four single blind-RCT (no. of subjects involved in active stimulation = 576; no. of subjects involved in sham protocol = 487). The most frequently treated pathology was major depressive episode/major depressive disorder, followed by resistant depression, bipolar depression and other MD. The majority of the studies used a repetitive TMS protocol, and the left dorsolateral prefrontal cortex was the main target area. Side effects were reported in eight studies and HMS (described as greater energy, insomnia, irritability, anxiety, suicidal attempt) in four studies. When comparing active TMS vs sham treatment, the risk of developing HMS was not significantly different between conditions.
CONCLUSION Applying the most usual protocols and the appropriate precautionary measures, TMS seems not to be related to HMS development.
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Affiliation(s)
- Andrea Miuli
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d'Annunzio” University of Chieti, Chieti 66100, Italy
| | - Gianna Sepede
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d'Annunzio” University of Chieti, Chieti 66100, Italy
| | - Gianfranco Stigliano
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d'Annunzio” University of Chieti, Chieti 66100, Italy
| | - Alessio Mosca
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d'Annunzio” University of Chieti, Chieti 66100, Italy
| | - Francesco Di Carlo
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d'Annunzio” University of Chieti, Chieti 66100, Italy
| | - Giacomo d’Andrea
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d'Annunzio” University of Chieti, Chieti 66100, Italy
| | - Aliseo Lalli
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d'Annunzio” University of Chieti, Chieti 66100, Italy
| | - Maria Chiara Spano
- Department of Psychiatry Affective Neuropsychiatry, Sahlgrenska University Hospital, Göteborg 40530, Sweden
| | - Mauro Pettorruso
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d'Annunzio” University of Chieti, Chieti 66100, Italy
| | - Giovanni Martinotti
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d'Annunzio” University of Chieti, Chieti 66100, Italy
- Department of Pharmacy, Clinical Science, University of Hertfordshire, Herts AL10 9AB, Italy
| | - Massimo di Giannantonio
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d'Annunzio” University of Chieti, Chieti 66100, Italy
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18
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Madore M, Poh E, Bolland SJ, Rivera J, Taylor J, Cheng J, Booth E, Nable M, Heath A, Yesavage J, Rodger J, McNerney MW. Moving back in the brain to drive the field forward: Targeting neurostimulation to different brain regions in animal models of depression and neurodegeneration. J Neurosci Methods 2021; 360:109261. [PMID: 34146593 PMCID: PMC8349553 DOI: 10.1016/j.jneumeth.2021.109261] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 05/22/2021] [Accepted: 06/13/2021] [Indexed: 01/28/2023]
Abstract
BACKGROUND Repetitive transcranial magnetic stimulation is a promising noninvasive therapeutic tool for a variety of brain-related disorders. However, most therapeutic protocols target the anterior regions, leaving many other areas unexplored. There is a substantial therapeutic potential for stimulating various brain regions, which can be optimized in animal models. NEW METHOD We illustrate a method that can be utilized reliably to stimulate the anterior or posterior brain in freely moving rodents. A coil support device is surgically attached onto the skull, which is used for consistent coil placement over the course of up to several weeks of stimulation sessions. RESULTS Our methods provide reliable stimulation in animals without the need for restraint or sedation. We see little aversive effects of support placement and stimulation. Computational models provide evidence that moving the coil support location can be utilized to target major stimulation sites in humans and mice. SUMMARY OF FINDINGS WITH THIS METHOD Animal models are key to optimizing brain stimulation parameters, but research relies on restraint or sedation for consistency in coil placement. The method described here provides a unique means for reliable targeted stimulation in freely moving animals. Research utilizing this method has uncovered changes in biochemical and animal behavioral measurements as a function of brain stimulation. CONCLUSIONS The majority of research on magnetic stimulation focuses on anterior regions. Given the substantial network connectivity throughout the brain, it is critical to develop a reliable method for stimulating different regions. The method described here can be utilized to better inform clinical trials about optimal treatment localization, stimulation intensity and number of treatment sessions, and provides a motivation for exploring posterior brain regions for both mice and humans.
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Affiliation(s)
- Michelle Madore
- Veterans Affairs Palo Alto Health Care system, Palo Alto, CA, USA,Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Eugenia Poh
- Experimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, Perth WA, Australia
| | - Samuel J Bolland
- Experimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, Perth WA, Australia
| | | | - Joy Taylor
- Veterans Affairs Palo Alto Health Care system, Palo Alto, CA, USA,Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Jauhtai Cheng
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Eric Booth
- Department of Electrical and Computer Engineering, Boise State University, Boise ID
| | - Monica Nable
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Alesha Heath
- Veterans Affairs Palo Alto Health Care system, Palo Alto, CA, USA,Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Jerry Yesavage
- Veterans Affairs Palo Alto Health Care system, Palo Alto, CA, USA,Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Jennifer Rodger
- Experimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, Perth WA, Australia
| | - M. Windy McNerney
- Veterans Affairs Palo Alto Health Care system, Palo Alto, CA, USA,Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
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Elyamany O, Leicht G, Herrmann CS, Mulert C. Transcranial alternating current stimulation (tACS): from basic mechanisms towards first applications in psychiatry. Eur Arch Psychiatry Clin Neurosci 2021; 271:135-156. [PMID: 33211157 PMCID: PMC7867505 DOI: 10.1007/s00406-020-01209-9] [Citation(s) in RCA: 120] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 10/27/2020] [Indexed: 12/11/2022]
Abstract
Transcranial alternating current stimulation (tACS) is a unique form of non-invasive brain stimulation. Sinusoidal alternating electric currents are delivered to the scalp to affect mostly cortical neurons. tACS is supposed to modulate brain function and, in turn, cognitive processes by entraining brain oscillations and inducing long-term synaptic plasticity. Therefore, tACS has been investigated in cognitive neuroscience, but only recently, it has been also introduced in psychiatric clinical trials. This review describes current concepts and first findings of applying tACS as a potential therapeutic tool in the field of psychiatry. The current understanding of its mechanisms of action is explained, bridging cellular neuronal activity and the brain network mechanism. Revisiting the relevance of altered brain oscillations found in six major psychiatric disorders, putative targets for the management of mental disorders using tACS are discussed. A systematic literature search on PubMed was conducted to report findings of the clinical studies applying tACS in patients with psychiatric conditions. In conclusion, the initial results may support the feasibility of tACS in clinical psychiatric populations without serious adverse events. Moreover, these results showed the ability of tACS to reset disturbed brain oscillations, and thus to improve behavioural outcomes. In addition to its potential therapeutic role, the reactivity of the brain circuits to tACS could serve as a possible tool to determine the diagnosis, classification or prognosis of psychiatric disorders. Future double-blind randomised controlled trials are necessary to answer currently unresolved questions. They may aim to detect response predictors and control for various confounding factors.
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Affiliation(s)
- Osama Elyamany
- Centre of Psychiatry, Justus-Liebig University, Klinikstrasse 36, 35392, Giessen, Hessen, Germany
- Centre for Mind, Brain and Behaviour (CMBB), University of Marburg and Justus-Liebig University Giessen, Marburg, Germany
| | - Gregor Leicht
- Department of Psychiatry and Psychotherapy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Christoph S Herrmann
- Experimental Psychology Lab, Centre for Excellence "Hearing4all," European Medical School, University of Oldenburg, Oldenburg, Lower Saxony, Germany
- Research Centre Neurosensory Science, University of Oldenburg, Oldenburg, Lower Saxony, Germany
| | - Christoph Mulert
- Centre of Psychiatry, Justus-Liebig University, Klinikstrasse 36, 35392, Giessen, Hessen, Germany.
- Centre for Mind, Brain and Behaviour (CMBB), University of Marburg and Justus-Liebig University Giessen, Marburg, Germany.
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Kullakçi H, Sonkaya AR. The Investigation of the Effects of Repetitive Transcranialmagnetic Stimulation Treatment on Taste and Smell Sensations in Depressed Patients. ACTA ACUST UNITED AC 2021; 58:26-33. [PMID: 33795949 DOI: 10.29399/npa.25087] [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: 03/03/2020] [Accepted: 08/18/2020] [Indexed: 11/07/2022]
Abstract
Introduction Loss in sense of smell and taste is a condition that can occur without an organic pathology and it is noteworthy in patients diagnosed with Major Depressive Disorder (MDD). Few studies have shown that Repetitive Transcranial Magnetic Stimulation (tTMS) can correct losses in sense of smell and taste. In this study, we aimed to examine the effects of tTMS treatment applied to patients diagnosed with MDD on the sense of smell and taste in this patient group. Methods The sense of smell of 56 patients who were diagnosed with MDD and had tTMS indication was examined with the "Sniffin' Sticks" smell test and the sense of taste with the "Taste Strips" taste test. MDD patients who lost at least one sense of smell and taste were included in the study, but a total of 30 patients were able to complete the study. Hamilton Depression Scale (HAM-D) was applied to the patients before tTMS treatment, and this scale was repeated after 15 sessions of tTMS treatment. Taste and smell senses were re-evaluated after the last tTMS session. Results According to the Sniffin Stick Smell test, 15 of 29 patients with hyposmia had normosmia after tTMS, and 16 of 18 patients who were found to have hypogeusia according to Taste Strips Taste test had Normogeusia after tTMS. There was a positive improvement in both the smell and taste scores of all patients who were treated, compared to before tTMS. The positive improvement in the smell tests of the patients who responded to the treatment according to the HAM-D scores was found to be significantly different than the patients who did not respond. Conclusion The positive effect of tTMS treatment on the sense of smell and taste has been demonstrated even in patients whose HAM-D scores could not be sufficiently decreased. In patients diagnosed with depression, using tTMS alone or adding it to the current treatment suggests that it may have a positive effect on the sense of smell and taste as well as depression treatment.
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Affiliation(s)
- Hakan Kullakçi
- Health Science University, Sultan Abdülhamid Han Training and Research Hospital, Department of Psychiatry, Istanbul, Turkey
| | - Ali Rıza Sonkaya
- Health Science University, Gülhane School of Medicine, Department of Neurology, Ankara, Turkey
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21
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Pettorruso M, Miuli A, Di Natale C, Montemitro C, Zoratto F, De Risio L, d'Andrea G, Dannon PN, Martinotti G, di Giannantonio M. Non-invasive brain stimulation targets and approaches to modulate gambling-related decisions: A systematic review. Addict Behav 2021; 112:106657. [PMID: 32987305 DOI: 10.1016/j.addbeh.2020.106657] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 08/23/2020] [Accepted: 09/10/2020] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Despite intense neuroscience research on the neurobiological underpinnings of Gambling Disorder (GD) and gambling-related decision-making, effective treatments targeting these dysfunctions are still lacking. Non Invasive Brain Stimulation (NIBS) techniques, such as transcranial Direct Current Stimulation (tDCS) and Transcranial Magnetic Stimulation (TMS), selectively modulate activity of brain circuits and have the potential to reverse alterations sustaining GD symptoms. Therefore, the aim of this systematic review was to determine the impact of different NIBS interventions on gambling-related decision processes. METHODS We conducted a comprehensive and translational search in three online databases (MEDLINE via PubMed, Scopus, Web of Science), in accordance with the PRISMA guidelines. We included studies applying neuromodulation (TMS, tDCS) techniques in GD patients or assessing gambling-related decision-making in healthy subjects. In addition, we explored the potential impact of NIBS in drug-induced GD (e.g., Parkinson's Disease). RESULTS Twenty-seven studies have been included. We summarized results to detect the impact of different targets and stimulation/inhibition protocols in terms of gambling-related decision-making. The majority of both tDCS and TMS studies targeted the dorsolateral prefrontal cortex. Although heterogeneous in protocols and parameters, results from tDCS and TMS studies converge in indicating that the stimulation (instead of inhibition) of prefrontal regions could be beneficial to contrast dysfunctional gambling-related decision processes. CONCLUSION NIBS interventions show promise to be further tested in controlled clinical settings for the treatment of behavioral addictions. Further studies are also necessary to investigate connectivity changes and laterality issues (unilateral versus bilateral; left versus right) of NIBS application in GD.
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Cho Y, Park J, Lee C, Lee S. Recent progress on peripheral neural interface technology towards bioelectronic medicine. Bioelectron Med 2020; 6:23. [PMID: 33292861 PMCID: PMC7706233 DOI: 10.1186/s42234-020-00059-z] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 11/05/2020] [Indexed: 11/23/2022] Open
Abstract
Modulation of the peripheral nervous system (PNS) has a great potential for therapeutic intervention as well as restore bodily functions. Recent interest has focused on autonomic nerves, as they regulate extensive functions implicated in organ physiology, chronic disease state and appear tractable to targeted modulation of discrete nerve units. Therapeutic interventions based on specific bioelectronic neuromodulation depend on reliable neural interface to stimulate and record autonomic nerves. Furthermore, the function of stimulation and recording requires energy which should be delivered to the interface. Due to the physiological and anatomical challenges of autonomic nerves, various forms of this active neural interface need to be developed to achieve next generation of neural interface for bioelectronic medicine. In this article, we present an overview of the state-of-the-art for peripheral neural interface technology in relation to autonomic nerves. Also, we reveal the current status of wireless neural interface for peripheral nerve applications. Recent studies of a novel concept of self-sustainable neural interface without battery and electronic components are presented. Finally, the recent results of non-invasive stimulation such as ultrasound and magnetic stimulation are covered and the perspective of the future research direction is provided.
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Affiliation(s)
- Youngjun Cho
- Daegu Geongbuk Institute of Science and Technology (DGIST), Daegu, 42899, Republic of Korea
| | - Jaeu Park
- Daegu Geongbuk Institute of Science and Technology (DGIST), Daegu, 42899, Republic of Korea
| | - Chengkuo Lee
- Electrical & Computer Engineering, National University of Singapore, Singapore, 117583, Singapore. .,Center for Intelligent Sensors and MEMS (CISM), National University of Singapore, Singapore, 117608, Singapore. .,NUS Graduate School for Integrated Science and Engineering (NGS), National University of Singapore, Singapore, 117456, Singapore.
| | - Sanghoon Lee
- Daegu Geongbuk Institute of Science and Technology (DGIST), Daegu, 42899, Republic of Korea.
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23
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Evaluation and Treatment of Vascular Cognitive Impairment by Transcranial Magnetic Stimulation. Neural Plast 2020. [PMID: 33193753 DOI: 10.1155/2020/8820881.] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
The exact relationship between cognitive functioning, cortical excitability, and synaptic plasticity in dementia is not completely understood. Vascular cognitive impairment (VCI) is deemed to be the most common cognitive disorder in the elderly since it encompasses any degree of vascular-based cognitive decline. In different cognitive disorders, including VCI, transcranial magnetic stimulation (TMS) can be exploited as a noninvasive tool able to evaluate in vivo the cortical excitability, the propension to undergo neural plastic phenomena, and the underlying transmission pathways. Overall, TMS in VCI revealed enhanced cortical excitability and synaptic plasticity that seem to correlate with the disease process and progression. In some patients, such plasticity may be considered as an adaptive response to disease progression, thus allowing the preservation of motor programming and execution. Recent findings also point out the possibility to employ TMS to predict cognitive deterioration in the so-called "brains at risk" for dementia, which may be those patients who benefit more of disease-modifying drugs and rehabilitative or neuromodulatory approaches, such as those based on repetitive TMS (rTMS). Finally, TMS can be exploited to select the responders to specific drugs in the attempt to maximize the response and to restore maladaptive plasticity. While no single TMS index owns enough specificity, a panel of TMS-derived measures can support VCI diagnosis and identify early markers of progression into dementia. This work reviews all TMS and rTMS studies on VCI. The aim is to evaluate how cortical excitability, plasticity, and connectivity interact in the pathophysiology of the impairment and to provide a translational perspective towards novel treatments of these patients. Current pitfalls and limitations of both studies and techniques are also discussed, together with possible solutions and future research agenda.
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24
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Balderston NL, Roberts C, Beydler EM, Deng ZD, Radman T, Luber B, Lisanby SH, Ernst M, Grillon C. A generalized workflow for conducting electric field-optimized, fMRI-guided, transcranial magnetic stimulation. Nat Protoc 2020; 15:3595-3614. [PMID: 33005039 PMCID: PMC8123368 DOI: 10.1038/s41596-020-0387-4] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Accepted: 07/22/2020] [Indexed: 12/27/2022]
Abstract
Transcranial magnetic stimulation (TMS) is a noninvasive method to stimulate the cerebral cortex that has applications in psychiatry, such as in the treatment of depression and anxiety. Although many TMS targeting methods that use figure-8 coils exist, many do not account for individual differences in anatomy or are not generalizable across target sites. This protocol combines functional magnetic resonance imaging (fMRI) and iterative electric-field (E-field) modeling in a generalized approach to subject-specific TMS targeting that is capable of optimizing the stimulation site and TMS coil orientation. To apply this protocol, the user should (i) operationally define a region of interest (ROI), (ii) generate the head model from the structural MRI data, (iii) preprocess the functional MRI data, (iv) identify the single-subject stimulation site within the ROI, and (iv) conduct E-field modeling to identify the optimal coil orientation. In comparison with standard targeting methods, this approach demonstrates (i) reduced variability in the stimulation site across subjects, (ii) reduced scalp-to-cortical-target distance, and (iii) reduced variability in optimal coil orientation. Execution of this protocol requires intermediate-level skills in structural and functional MRI processing. This protocol takes ~24 h to complete and demonstrates how constrained fMRI targeting combined with iterative E-field modeling can be used as a general method to optimize both the TMS coil site and its orientation.
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Affiliation(s)
- Nicholas L Balderston
- Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
- Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
| | - Camille Roberts
- Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
| | - Emily M Beydler
- Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
| | - Zhi-De Deng
- Noninvasive Neuromodulation Unit, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
| | - Thomas Radman
- Noninvasive Neuromodulation Unit, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
| | - Bruce Luber
- Noninvasive Neuromodulation Unit, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
| | - Sarah H Lisanby
- Noninvasive Neuromodulation Unit, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
| | - Monique Ernst
- Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
| | - Christian Grillon
- Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
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25
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Koponen LM, Goetz SM, Tucci DL, Peterchev AV. Sound comparison of seven TMS coils at matched stimulation strength. Brain Stimul 2020; 13:873-880. [PMID: 32289720 PMCID: PMC7263763 DOI: 10.1016/j.brs.2020.03.004] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 02/11/2020] [Accepted: 03/04/2020] [Indexed: 11/30/2022] Open
Abstract
Background: Accurate data on the sound emitted by transcranial magnetic stimulation (TMS) coils is lacking. Methods: We recorded the sound waveforms of seven coils with high bandwidth. We estimated the neural stimulation strength by measuring the induced electric field and applying a strengtheduration model to account for different waveforms. Results: Across coils, at maximum stimulator output and 25 cm distance, the sound pressure level (SPL) was 98–125 dB(Z) per pulse and 76–98 dB(A) for a 20 Hz pulse train. At 5 cm distance, these values were estimated to increase to 112–139 dB(Z) and 90–112 dB(A), respectively. Conclusions: The coils’ airborne sound can exceed some exposure limits for TMS subjects and, in some cases, for operators. These findings are consistent with the current TMS safety guidelines that recommend the use of hearing protection.
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Affiliation(s)
- Lari M Koponen
- Department of Psychiatry & Behavioral Sciences, Duke University, Durham, NC, 27710, USA
| | - Stefan M Goetz
- Department of Psychiatry & Behavioral Sciences, Duke University, Durham, NC, 27710, USA; Department of Electrical & Computer Engineering, Duke University, Durham, NC, 27708, USA; Department of Neurosurgery, Duke University, Durham, NC, 27710, USA
| | - Debara L Tucci
- Department of Head and Neck Surgery & Communication Sciences, Duke University, Durham, NC, 27710, USA
| | - Angel V Peterchev
- Department of Psychiatry & Behavioral Sciences, Duke University, Durham, NC, 27710, USA; Department of Electrical & Computer Engineering, Duke University, Durham, NC, 27708, USA; Department of Neurosurgery, Duke University, Durham, NC, 27710, USA; Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA.
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26
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Moretti J, Poh EZ, Rodger J. rTMS-Induced Changes in Glutamatergic and Dopaminergic Systems: Relevance to Cocaine and Methamphetamine Use Disorders. Front Neurosci 2020; 14:137. [PMID: 32210744 PMCID: PMC7068681 DOI: 10.3389/fnins.2020.00137] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Accepted: 02/03/2020] [Indexed: 12/12/2022] Open
Abstract
Cocaine use disorder and methamphetamine use disorder are chronic, relapsing disorders with no US Food and Drug Administration-approved interventions. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation tool that has been increasingly investigated as a possible therapeutic intervention for substance use disorders. rTMS may have the ability to induce beneficial neuroplasticity in abnormal circuits and networks in individuals with addiction. The aim of this review is to highlight the rationale and potential for rTMS to treat cocaine and methamphetamine dependence: we synthesize the outcomes of studies in healthy humans and animal models to identify and understand the neurobiological mechanisms of rTMS that seem most involved in addiction, focusing on the dopaminergic and glutamatergic systems. rTMS-induced changes to neurotransmitter systems include alterations to striatal dopamine release and metabolite levels, as well as to glutamate transporter and receptor expression, which may be relevant for ameliorating the aberrant plasticity observed in individuals with substance use disorders. We also discuss the clinical studies that have used rTMS in humans with cocaine and methamphetamine use disorders. Many such studies suggest changes in network connectivity following acute rTMS, which may underpin reduced craving following chronic rTMS. We suggest several possible future directions for research relating to the therapeutic potential of rTMS in addiction that would help fill current gaps in the literature. Such research would apply rTMS to animal models of addiction, developing a translational pipeline that would guide evidence-based rTMS treatment of cocaine and methamphetamine use disorder.
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Affiliation(s)
- Jessica Moretti
- Experimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, Crawley, WA, Australia.,School of Human Sciences, The University of Western Australia, Crawley, WA, Australia.,Brain Plasticity Group, Perron Institute for Neurological and Translational Science, Nedlands, WA, Australia
| | - Eugenia Z Poh
- Experimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, Crawley, WA, Australia.,School of Human Sciences, The University of Western Australia, Crawley, WA, Australia.,Brain Plasticity Group, Perron Institute for Neurological and Translational Science, Nedlands, WA, Australia
| | - Jennifer Rodger
- Experimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, Crawley, WA, Australia.,Brain Plasticity Group, Perron Institute for Neurological and Translational Science, Nedlands, WA, Australia
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27
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Kassie S, Ali O, Luthra V, Karrani A, Orr K, Alsaadi T, Arida A. Repetitive transcranial magnetic stimulation in the treatment of major depressive disorder: Preliminary results from the United Arab Emirates. HAMDAN MEDICAL JOURNAL 2020. [DOI: 10.4103/hmj.hmj_37_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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28
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Cantone M, Lanza G, Fisicaro F, Pennisi M, Bella R, Di Lazzaro V, Di Pino G. Evaluation and Treatment of Vascular Cognitive Impairment by Transcranial Magnetic Stimulation. Neural Plast 2020; 2020:8820881. [PMID: 33193753 PMCID: PMC7641667 DOI: 10.1155/2020/8820881] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 09/23/2020] [Accepted: 10/12/2020] [Indexed: 02/07/2023] Open
Abstract
The exact relationship between cognitive functioning, cortical excitability, and synaptic plasticity in dementia is not completely understood. Vascular cognitive impairment (VCI) is deemed to be the most common cognitive disorder in the elderly since it encompasses any degree of vascular-based cognitive decline. In different cognitive disorders, including VCI, transcranial magnetic stimulation (TMS) can be exploited as a noninvasive tool able to evaluate in vivo the cortical excitability, the propension to undergo neural plastic phenomena, and the underlying transmission pathways. Overall, TMS in VCI revealed enhanced cortical excitability and synaptic plasticity that seem to correlate with the disease process and progression. In some patients, such plasticity may be considered as an adaptive response to disease progression, thus allowing the preservation of motor programming and execution. Recent findings also point out the possibility to employ TMS to predict cognitive deterioration in the so-called "brains at risk" for dementia, which may be those patients who benefit more of disease-modifying drugs and rehabilitative or neuromodulatory approaches, such as those based on repetitive TMS (rTMS). Finally, TMS can be exploited to select the responders to specific drugs in the attempt to maximize the response and to restore maladaptive plasticity. While no single TMS index owns enough specificity, a panel of TMS-derived measures can support VCI diagnosis and identify early markers of progression into dementia. This work reviews all TMS and rTMS studies on VCI. The aim is to evaluate how cortical excitability, plasticity, and connectivity interact in the pathophysiology of the impairment and to provide a translational perspective towards novel treatments of these patients. Current pitfalls and limitations of both studies and techniques are also discussed, together with possible solutions and future research agenda.
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Affiliation(s)
- Mariagiovanna Cantone
- 1Department of Neurology, Sant'Elia Hospital, ASP Caltanissetta, Caltanissetta 93100, Italy
| | - Giuseppe Lanza
- 2Department of Surgery and Medical-Surgical Specialties, University of Catania, Catania 95123, Italy
- 3Department of Neurology IC, Oasi Research Institute–IRCCS, Troina 94108, Italy
| | - Francesco Fisicaro
- 4Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95123, Italy
| | - Manuela Pennisi
- 4Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95123, Italy
| | - Rita Bella
- 5Department of Medical and Surgical Sciences and Advanced Technologies, University of Catania, Catania 95123, Italy
| | - Vincenzo Di Lazzaro
- 6Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, Università Campus Bio-Medico di Roma, Rome 00128, Italy
| | - Giovanni Di Pino
- 7Research Unit of Neurophysiology and Neuroengineering of Human-Technology Interaction (NeXTlab), Università Campus Bio-Medico di Roma, Rome 00128, Italy
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29
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Malone LA, Sun LR. Transcranial Magnetic Stimulation for the Treatment of Pediatric Neurological Disorders. Curr Treat Options Neurol 2019; 21:58. [PMID: 31720969 DOI: 10.1007/s11940-019-0600-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
PURPOSE OF REVIEW Repetitive transcranial magnetic stimulation (rTMS) is a form of noninvasive brain stimulation that is used for the treatment of migraine and major depression in adults and is now being evaluated for use in other disorders. The purpose of this review is to summarize the physiology underlying TMS, the safety and tolerability in pediatric patients, and the evidence for TMS efficacy in the treatment of pediatric neurologic disorders. RECENT FINDINGS Studies investigating rTMS for adolescent depression, hemiparesis due to pediatric stroke, autism, and tics/Tourette syndrome have demonstrated some therapeutic benefit. rTMS has been insufficiently studied for migraine in children despite benefits demonstrated for adult migraine. Evidence for rTMS in childhood epilepsy and ADHD remains mixed. Repetitive transcranial magnetic stimulation is emerging as a safe, tolerable, and potentially effective therapeutic strategy in a number of pediatric neurological disorders, though high-quality, randomized controlled trials are needed. Ongoing studies should focus on optimization of treatment protocols, development of biomarkers to identify children who will benefit from the technique, and identification of the most appropriate indicators of response.
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Affiliation(s)
- Laura A Malone
- Department of Neurology, Johns Hopkins University School of Medicine, 200 N. Wolfe Street, Suite 2158, Baltimore, MD, 21287, USA
| | - Lisa R Sun
- Department of Neurology, Johns Hopkins University School of Medicine, 200 N. Wolfe Street, Suite 2158, Baltimore, MD, 21287, USA.
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da Silva Júnior HB, Fernandes MR, Souza ÂMC. Repetitive Transcranial Magnetic Stimulation Improves Depressive Symptoms and Quality of Life of Poststroke Patients-Prospective Case Series Study. J Cent Nerv Syst Dis 2019; 11:1179573519871304. [PMID: 31488959 PMCID: PMC6710684 DOI: 10.1177/1179573519871304] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Accepted: 07/31/2019] [Indexed: 01/10/2023] Open
Abstract
Background: Poststroke depression (PSD) is a serious psychiatric complication often reported after a stroke. Nearly a third of stroke survivors experience depressive symptoms at some point, affecting their functional recovery and quality of life. In recent years, repetitive transcranial magnetic stimulation (rTMS) has been studied by many researchers and found to be a safe supporting tool for the treatment of PSD. Objective: We aim to evaluate the effects of rTMS on PSD and on the quality of life of poststroke patients. Method: A prospective clinical case series, performed at CRER Rehabilitation, Brazil, between June 2016 and May 2017. A nonprobabilistic sample (n = 15) was divided into 2 groups (excitatory stimulation in F3, n = 8; inhibitory stimulation in F4, n = 7) and underwent 20 sessions of rTMS. Individuals were assessed according to the 17-item Hamilton Depression Rating Scale (HAM-D17) and World Health Organization Quality of Life-Brief Version (WHOQOL-BREF) questionnaire at 3 different moments: baseline, at the end of the treatment, and in a 1-month follow-up meeting. Results: Both groups presented a significant change in the score of all WHOQOL-BREF domains and in HAM-D17. In the group that received inhibitory stimulation (F4), score changes were continuous and gradual, comparing the 3 moments. In the excitatory stimulated (F3) group, however, the improvement in scores was more expressive between baseline and the second moment, without significant changes in the follow-up. Conclusions: The findings of this clinical study suggest that rTMS can be a promising tool, capable of relieving depressive symptoms and helping in the improvement of poststroke patients’ quality of life.
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31
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Leung TK, Lee CM, Gasbarri M, Chen YC. Base on concept of traditional Chinese medicine: Experimental studies on efficacy of BIOCERAMIC Resonance to alleviate drug withdrawal symptoms. J Tradit Complement Med 2019; 9:257-262. [PMID: 31453120 PMCID: PMC6702142 DOI: 10.1016/j.jtcme.2018.01.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2017] [Revised: 01/09/2018] [Accepted: 01/11/2018] [Indexed: 12/19/2022] Open
Abstract
Those who are challenged by dependency on prescription drugs or suffer drug addictions have few options available to them for recovery, such as psychotherapy and physiotherapy. Here we present a new approach with clinical examples involving stimulant addiction or overdose of hypnotic drugs that were received BIOCERAMIC Resonance, which was developed based on concept of 12 meridian channels of traditional Chinese medicine, and has successful withdrawal or dose reduction benefits. We describe the whole process and the clinical outcome. And by help of our previous publication on functional MRI, we discuss the possible brain locations response to BIOCERAMIC Resonance that may be corresponding to the beneficial effects of relief of depression, sleep deprivation and other mental symptoms that associate with substance abuse and withdrawal effects. We suggest this could be potentially widely application on substances abuse.
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Cui H, Ren R, Lin G, Zou Y, Jiang L, Wei Z, Li C, Wang G. Repetitive Transcranial Magnetic Stimulation Induced Hypoconnectivity Within the Default Mode Network Yields Cognitive Improvements in Amnestic Mild Cognitive Impairment: A Randomized Controlled Study. J Alzheimers Dis 2019; 69:1137-1151. [PMID: 31127779 DOI: 10.3233/jad-181296] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Affiliation(s)
- Hailun Cui
- Department of Neurology & Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Rujing Ren
- Department of Neurology & Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Guozhen Lin
- Department of Psychiatry, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yang Zou
- Department of Neurology & Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lijuan Jiang
- Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhengde Wei
- Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Key Laboratory of Brain Function and Disease, Chinese Academy of Sciences, School of Life Sciences, University of Science & Technology of China, Hefei, Anhui, China
| | - Chunbo Li
- Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
- CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, Shanghai, China
| | - Gang Wang
- Department of Neurology & Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Lucena MFG, Teixeira PEP, Bonin Pinto C, Fregni F. Top 100 cited noninvasive neuromodulation clinical trials. Expert Rev Med Devices 2019; 16:451-466. [PMID: 31092060 DOI: 10.1080/17434440.2019.1615440] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
INTRODUCTION Introduction: Transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) are noninvasive neuromodulation techniques used as therapeutic and research tools for several neuropsychiatric conditions. Given the exponential scientific growth of this field, we aimed to systematically review the most cited clinical trials using TMS or tDCS. AREAS COVERED A de-novo keyword search strategy identified and characterized the 100 most-cited trials. Total citation count for the most cited trials was 13,204. Articles were published between 2008 and 2014 in 50 different journals with a median impact factor of 6.52 (IQR 3.37). Almost half of the top cited papers were investigating mechanisms of action in healthy subjects. Most studies were feasibility trials and only five were pivotal trials, including the ones used for recent FDA approval. Seven articles were interlinked with another article by at least 25 citations and eight authors had collaborated with at least one other author. EXPERT OPINION Although there has been a significant increase in interest for rTMS and tDCS, most of the cited clinical trials are still small feasibility studies, what reinforced the need for more robust clinical trials (larger samples sizes and effects sizes) to better define clinical effectiveness.
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Affiliation(s)
- Mariana F G Lucena
- a Laboratory of Neuromodulation & Center for Clinical Research Learning, Physics and Rehabilitation Department , Spaulding Rehabilitation Hospital, Harvard Medical School , Boston , MA USA
| | - Paulo E P Teixeira
- a Laboratory of Neuromodulation & Center for Clinical Research Learning, Physics and Rehabilitation Department , Spaulding Rehabilitation Hospital, Harvard Medical School , Boston , MA USA.,b Research and Education Center , Wilson Mello Institute , Campinas, Sao Paulo , Brazil
| | - Camila Bonin Pinto
- a Laboratory of Neuromodulation & Center for Clinical Research Learning, Physics and Rehabilitation Department , Spaulding Rehabilitation Hospital, Harvard Medical School , Boston , MA USA.,c Department of Neuroscience and Behavior, Psychology Institute , University of Sao Paulo , Sao Paulo , Brazil
| | - Felipe Fregni
- a Laboratory of Neuromodulation & Center for Clinical Research Learning, Physics and Rehabilitation Department , Spaulding Rehabilitation Hospital, Harvard Medical School , Boston , MA USA
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Manzardo AM, Ely B, Davila MC. Time to remission analysis for major depressive disorder after repetitive transcranial magnetic stimulation (rTMS). Ment Illn 2019; 11:8141. [PMID: 31281611 PMCID: PMC6589537 DOI: 10.4081/mi.2019.8141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Indexed: 11/23/2022] Open
Abstract
We previously examined the efficacy of rTMS for major depressive disorder in an applied clinical practice. Clinical response was related to severity of depression as well as the rTMS instrument utilized suggesting a relationship to instrument or magnetic field parameters and individual factors. The effectiveness of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depressive disorder was further evaluated using Log-Rank statistics for time to remission outcomes. A follow-up retrospective medical records study was carried out on patients with major depressive disorder undergoing rTMS therapy at AwakeningsKC Clinical Neuroscience Institute (CNI), a suburban tertiary psychiatric clinic. Cox Proportional Hazard with Log-Rank statistics were applied and the time course to clinical remission was evaluated over a 6-week period with respect to age, gender, and depression severity. Clinical response was observed referencing two different rTMS instruments (MagVenture; NeuroStar). Time to remission studies of 247 case reports (N=98 males; N=149 females) showed consistently greater clinically defined remission rates after 6 weeks of rTMS treatment for patients using the MagVenture vs NeuroStar instrument. Patients previously admitted for inpatient psychiatric hospitalization exhibited higher response rates when treated with the MagVenture rTMS unit. Stepwise Cox Proportional Hazards Regression final model of time to remission included rTMS unit, inpatient psychiatric hospitalization and obese body habitus. Response to rTMS in applied clinical practice is related to severity of psychiatric illness and may require consideration of magnetic field parameters of the rTMS unit with respect to individual factors such as sex or body composition.
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Affiliation(s)
- Ann M Manzardo
- Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center, KS
| | - Brianna Ely
- Awakenings KC Clinical Neuroscience Institute, KS, USA
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Davila MC, Ely B, Manzardo AM. Repetitive transcranial magnetic stimulation (rTMS) using different TMS instruments for major depressive disorder at a suburban tertiary clinic. Ment Illn 2019; 11:7947. [PMID: 31007881 PMCID: PMC6452224 DOI: 10.4081/mi.2019.7947] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2018] [Indexed: 12/21/2022] Open
Abstract
Repetitive transcranial magnetic stimulation (rTMS) is a neurostimulatory technique used to modulate orbital frontal corticostriatal (OFC) activity and clinical symptomatology for psychiatric disorders involving OFC dysfunction. We examined the effectiveness of rTMS in the treatment of major depressive disorder in an applied clinical setting (Awakening KC CNI) to assess efficacy and optimize rTMS parameters within clinical practice. A retrospective review of medical records was carried out on patients with major depressive disorder undergoing rTMS therapy at Awakenings KC Clinical Neuroscience Institute (CNI), a suburban tertiary psychiatric clinic. A detailed de-identified data set of clinical outcomes was compiled. Patient Health Questionnaire 9 (PHQ-9) total score, clinical remission rate and week achieved were evaluated over 6 weeks of treatment to assess clinical response referencing two different rTMS instruments (MagVenture; NeuroStar). Our survey included 247 participants from males (N=98) and females (N=149) with average baseline PHQ-9 scores of 21.7±4, classified as severe depression. Clinically rated remission rates of 72% were achieved in 3.1±1.0 weeks and associated with prior history of psychiatric hospitalization, suicide attempts and substance use disorder. Average baseline PHQ- 9 scores decreased significantly over time with proportionately greater remission rates achieved for patients treated using the MagVenture over NeuroStar instrument. rTMS in applied clinical practice is efficacious over a wide range of settings and patients. Clinical response was related to severity of depression symptoms (e.g., prior hospitalization; suicide attempts) validating efficacy in critically ill groups. Clinical response may be impacted by rTMS instrument, magnetic field parameters or individual factors.
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Affiliation(s)
| | - Brianna Ely
- Awakenings KC Clinical Neuroscience Institute, KS
| | - Ann M Manzardo
- Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center, KS, USA
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Davila MC, Ely B, Manzardo AM. Relationship between body mass and clinical response to repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder. Ment Illn 2019; 11:8116. [PMID: 31281609 PMCID: PMC6589535 DOI: 10.4081/mi.2019.8116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Indexed: 12/03/2022] Open
Abstract
Repetitive transcranial magnetic stimulation (rTMS) has been proven to be efficacious in the treatment of Major Depressive Disorder (MDD). We previously examined the effectiveness of rTMS for MDD in an applied clinical setting, AwakeningsKC Clinical Neuroscience Institute (CNI) and found high remission rates for patients diagnosed with MDD following rTMS treatment. An unexpected relationship with body composition and rTMS unit was discovered. This sub-study extends the previous investigation through a focused analysis of the effects of body composition on response to rTMS in the treatment of MDD. We utilized data collected from a retrospective review of medical records for patients diagnosed with MDD undergoing rTMS therapy at AwakeningsKC CNI. Patient Health Questionnaire 9 (PHQ-9) scores, time to remission status and body mass index (BMI) at baseline were considered while referencing two different rTMS instruments (MagVenture; NeuroStar). We found 23 (9%) of 247 participants met criteria for obese status (BMI≥30) with an average baseline PHQ-9 score of 22±4, classified as “severe depression”. Obesity status was differentially impacted by the rTMS instrument used for treatment. Patients with obesity showed a shorter time to remission (mean 2.7±0.27 vs. mean 3.4±0.3 weeks) and proportionately greater remission rate (100% vs. 71%) when treated using the MagVenture relative to the NeuroStar instrument. Clinical response to rTMS therapy for MDD appears to be guided by individual factors including body composition and rTMS parameters such as the unit used for treatment. Further study of these influences could aid in the optimization of clinical response to rTMS.
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Affiliation(s)
| | - Brianna Ely
- Awakenings KC Clinical Neuroscience Institute, KS
| | - Ann M Manzardo
- Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center, KS, USA
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Garnaat SL, Yuan S, Wang H, Philip NS, Carpenter LL. Updates on Transcranial Magnetic Stimulation Therapy for Major Depressive Disorder. Psychiatr Clin North Am 2018; 41:419-431. [PMID: 30098655 PMCID: PMC6979370 DOI: 10.1016/j.psc.2018.04.006] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Transcranial magnetic stimulation has emerged as a treatment option for treatment-resistant depression. While existing data largely support efficacy of transcranial magnetic stimulation for major depressive disorder, ongoing research aims to optimize treatment parameters and identify biomarkers of treatment response. In this article, the authors describe data from controlled trials and ongoing efforts to enhance transcranial magnetic stimulation outcomes for major depressive disorder. Findings from preliminary research aimed at identifying neuroimaging and neurophysiological biomarkers of transcranial magnetic stimulation effects are discussed.
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Affiliation(s)
- Sarah L. Garnaat
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA,Butler Hospital, Providence, RI, USA
| | - Shiwen Yuan
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
| | - Haizhi Wang
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
| | - Noah S. Philip
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA,Butler Hospital, Providence, RI, USA,Providence VA Medical Center, Providence, RI, USA
| | - Linda L. Carpenter
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA,Butler Hospital, Providence, RI, USA
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Weigand A, Horn A, Caballero R, Cooke D, Stern AP, Taylor SF, Press D, Pascual-Leone A, Fox MD. Prospective Validation That Subgenual Connectivity Predicts Antidepressant Efficacy of Transcranial Magnetic Stimulation Sites. Biol Psychiatry 2018; 84:28-37. [PMID: 29274805 PMCID: PMC6091227 DOI: 10.1016/j.biopsych.2017.10.028] [Citation(s) in RCA: 283] [Impact Index Per Article: 40.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Revised: 10/07/2017] [Accepted: 10/31/2017] [Indexed: 01/27/2023]
Abstract
BACKGROUND The optimal target in the dorsolateral prefrontal cortex for treating depression with repetitive transcranial magnetic stimulation (rTMS) remains unknown. Better efficacy has been associated with stimulation sites that are 1) more anterior and lateral and 2) more functionally connected to the subgenual cingulate. Here we prospectively test whether these factors predict response in individual patients. METHODS A primary cohort (Boston, n = 25) with medication-refractory depression underwent conventional open-label rTMS to the left dorsolateral prefrontal cortex. A secondary cohort (Michigan, n = 16) underwent 4 weeks of sham followed by open-label rTMS for nonresponders (n = 12). In each patient, the location of the stimulation site was recorded with frameless stereotaxy. Connectivity between each patient's stimulation site and the subgenual cingulate was assessed using resting-state functional connectivity magnetic resonance imaging from a cohort of healthy subjects (n = 1000) and confirmed using connectivity from patients with depression (n = 38). RESULTS In our primary cohort, antidepressant efficacy was predicted by stimulation sites that were both more anterolateral (r = .51, p < .01) and more negatively correlated with the subgenual cingulate (r = -.55, p < .005). However, subgenual connectivity was the only independent predictor of response and the only factor to predict response to active (r = -.52, p < .05) but not sham rTMS in our secondary cohort. CONCLUSIONS This study provides prospective validation that functional connectivity between an individual's rTMS cortical target and the subgenual cingulate predicts antidepressant response. Implications for improving the cortical rTMS target for depression are discussed.
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Affiliation(s)
- Anne Weigand
- Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215,Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Luisenstrasse 56, 10099 Berlin, Germany
| | - Andreas Horn
- Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215,Department of Neurology, Movement Disorder and Neuromodulation Unit, Charité – Universitätsmedizin, Berlin, Germany
| | - Ruth Caballero
- Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215,Bioengineering and Telemedicine Center, ETSI Telecomunicación, Universidad Politécnica de Madrid, Avenida Complutense No 30 Ciudad Universitaria, 28040 Madrid, Spain
| | - Danielle Cooke
- Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215
| | - Adam P. Stern
- Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215,Division of Cognitive Neurology, Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215
| | - Stephan F. Taylor
- Department of Psychiatry, University of Michigan, Ann Arbor, MI, 48109
| | - Daniel Press
- Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215,Division of Cognitive Neurology, Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215
| | - Alvaro Pascual-Leone
- Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215,Division of Cognitive Neurology, Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215,Institut Guttmann, Universitat Autonoma de Barcelona, Badalona, Barcelona, Spain
| | - Michael D. Fox
- Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215,Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114,Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129,Corresponding author.
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Cocchi L, Zalesky A, Nott Z, Whybird G, Fitzgerald PB, Breakspear M. Transcranial magnetic stimulation in obsessive-compulsive disorder: A focus on network mechanisms and state dependence. NEUROIMAGE-CLINICAL 2018; 19:661-674. [PMID: 30023172 PMCID: PMC6047114 DOI: 10.1016/j.nicl.2018.05.029] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Revised: 05/21/2018] [Accepted: 05/22/2018] [Indexed: 02/07/2023]
Abstract
Background Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique that has shown promise as an adjunct treatment for the symptoms of Obsessive-Compulsive Disorder (OCD). Establishing a clear clinical role for TMS in the treatment of OCD is contingent upon evidence of significant efficacy and reliability in reducing symptoms. Objectives We present the basic principles supporting the effects of TMS on brain activity with a focus on network-based theories of brain function. We discuss the promises and pitfalls of this technique as a means of modulating brain activity and reducing OCD symptoms. Methods Synthesis of trends and critical perspective on the potential benefits and limitations of TMS interventions in OCD. Findings Our critical synthesis suggests the need to better quantify the role of TMS in a clinical setting. The context in which the stimulation is performed, the neural principles supporting the effects of local stimulation on brain networks, and the heterogeneity of neuroanatomy are often overlooked in the clinical application of TMS. The lack of consideration of these factors may partly explain the variable efficacy of TMS interventions for OCD symptoms. Conclusions Results from existing clinical studies and emerging knowledge about the effects of TMS on brain networks are encouraging but also highlight the need for further research into the use of TMS as a means of selectively normalising OCD brain network dynamics and reducing related symptoms. The combination of neuroimaging, computational modelling, and behavioural protocols known to engage brain networks affected by OCD has the potential to improve the precision and therapeutic efficacy of TMS interventions. The efficacy of this multimodal approach remains, however, to be established and its effective translation in clinical contexts presents technical and implementation challenges. Addressing these practical, scientific and technical issues is required to assess whether OCD can take its place alongside major depressive disorder as an indication for the use of TMS.
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Affiliation(s)
- Luca Cocchi
- QIMR Berghofer Medical Research Institute, Brisbane, Australia.
| | - Andrew Zalesky
- Melbourne Neuropsychiatry Centre, University of Melbourne, Melbourne, Australia; Department of Biomedical Engineering, University of Melbourne, Melbourne, Australia
| | - Zoie Nott
- QIMR Berghofer Medical Research Institute, Brisbane, Australia
| | | | - Paul B Fitzgerald
- Epworh Clinic Epworth Healthcare, Camberwell, Victoria Australia and the MAPrc, Monash University Central Clinical School and The Alfred, Melbourne, Australia
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Abstract
PURPOSE OF REVIEW This article aims to review select applications of Transcranial Magnetic Stimulation (TMS) that have significant relevance in geriatric psychiatry. RECENT FINDINGS Small study sizes and parameter variability limit the generalizability of many TMS studies in geriatric patients. Additionally, geriatric patients have unique characteristics that can moderate the efficacy of TMS. Nonetheless, several promising experimental applications in addition to the FDA-approved indication for major depression have emerged. Cognitive impairment, neuropathic pain, and smoking cessation are experimental applications with special significance to the elderly. Cognitive impairment has been researched the most in this population and evidence thus far suggests that TMS has potential therapeutic benefit. There is also evidence to suggest benefit from TMS for neuropathic pain and smoking cessation in working age adults. TMS is consistently reported as a safe and well-tolerated treatment modality with no adverse cognitive side effects. TMS is a safe treatment modality that can be effective for certain applications in the elderly. Additional research that specifically includes older subjects is needed to replicate findings and to optimize treatment protocols for this population.
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Affiliation(s)
- Ilva G Iriarte
- Department of Psychiatry, Medical University of South Carolina (MUSC), Charleston, SC, USA.
| | - Mark S George
- Department of Psychiatry, Medical University of South Carolina (MUSC), Charleston, SC, USA.,Ralph H. Johnson VA Medical Center, Charleston, SC, USA
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VanDerwerker CJ, Ross RE, Stimpson KH, Embry AE, Aaron SE, Cence B, George MS, Gregory CM. Combining therapeutic approaches: rTMS and aerobic exercise in post-stroke depression: a case series. Top Stroke Rehabil 2018; 25:61-67. [PMID: 28982298 PMCID: PMC5801693 DOI: 10.1080/10749357.2017.1374685] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Accepted: 08/29/2017] [Indexed: 12/28/2022]
Abstract
Objective and importance Residual effects of stroke include well-documented functional limitations and high prevalence of depression. Repetitive transcranial magnetic stimulation (rTMS) and aerobic exercise (AEx) are established techniques that improve depressive symptoms, but a combination of the two has yet to be reported. The purpose of this case series is to examine the safety, feasibility, and impact of combined rTMS and AEx on post-stroke depression and functional mobility. Clinical presentation Three participants with a history of stroke and at least mild depressive symptoms (Patient Health Questionare-9 ≥5). Intervention Both rTMS and AEx were completed 3 times/week for 8-weeks. rTMS was applied to the left dorsolateral prefrontal cortex, 5000 pulses/session at 10 Hz, at an intensity of 120% of resting motor threshold. AEx consisted of 40 min of treadmill walking at 50-70% of heart rate reserve. Results Depressive symptoms improved in all three participants, with all demonstrating response (≥50% improvement in symptoms) and likely remission. All participants improved their Six Minute Walk Test distance and Participants 1 and 2 also improved Berg Balance Scale scores. Participants 1 and 3 improved overground walking speeds. No serious adverse events occurred with the application of rTMS or AEx and the participants' subjective reports indicated positive responses. Adherence rate for both rTMS and AEx was 98%. Conclusion Combined treatment of rTMS and AEx appears safe, feasible, and tolerable in individuals with a history of stroke and at least mild depressive symptoms. All participants had good compliance and demonstrated improvements in both depressive symptoms and walking capacity.
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Affiliation(s)
- Catherine J. VanDerwerker
- Department of Health Sciences and Research, Medical University of South Carolina, Charleston, SC, USA
| | - Ryan E. Ross
- Department of Health Sciences and Research, Medical University of South Carolina, Charleston, SC, USA
| | - Katy H. Stimpson
- Department of Psychiatry, Stanford University, Stanford, CA, USA
| | - Aaron E. Embry
- Department of Health Sciences and Research, Medical University of South Carolina, Charleston, SC, USA
| | - Stacey E. Aaron
- Department of Health Sciences and Research, Medical University of South Carolina, Charleston, SC, USA
| | - Brian Cence
- Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA
| | - Mark S. George
- Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA
- Brain Stimulation Division, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA
- Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA
| | - Chris M. Gregory
- Department of Health Sciences and Research, Medical University of South Carolina, Charleston, SC, USA
- Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA
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Effect of Threat on Right dlPFC Activity during Behavioral Pattern Separation. J Neurosci 2017; 37:9160-9171. [PMID: 28842415 DOI: 10.1523/jneurosci.0717-17.2017] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2017] [Revised: 07/14/2017] [Accepted: 07/20/2017] [Indexed: 01/29/2023] Open
Abstract
It has long been established that individuals with anxiety disorders tend to overgeneralize attributes of fearful stimuli to nonfearful stimuli, but there is little mechanistic understanding of the neural system that supports overgeneralization. To address this gap in our knowledge, this study examined effect of experimentally induced anxiety in humans on generalization using the behavioral pattern separation (BPS) paradigm. Healthy subjects of both sexes encoded and retrieved novel objects during periods of safety and threat of unpredictable shocks while we recorded brain activity with fMRI. During retrieval, subjects were instructed to differentiate among new, old, and altered images. We hypothesized that the hippocampus and dorsolateral prefrontal cortex (dlPFC) would play a key role in the effect of anxiety on BPS. The dlPFC, but not the hippocampus, showed increased activity for altered images compared with old images when retrieval occurred during periods of threat compared with safety. In addition, accuracy for altered items retrieved during threat was correlated with dlPFC activity. Together, these results suggest that overgeneralization in anxiety patients may be mediated by an inability to recruit the dlPFC, which mediates the cognitive control needed to overcome anxiety and differentiate between old and altered items during periods of threat.SIGNIFICANCE STATEMENT Anxiety and posttraumatic stress disorder patients generalize fear to nonfearful fear stimuli, making it difficult to regulate anxiety. Understanding how anxiety affects generalization is key to understanding the overgeneralization experienced by these patients. We examined this relationship in healthy subjects by studying how threat of shock affects neural responses to previously encountered stimuli. Although previous studies point to hippocampal involvement, we found that threat affected activity in the dorsolateral prefrontal cortex (dlPFC), rather than the hippocampus, when subjects encountered slightly altered versions of the previously encountered items. Importantly, this dlPFC activity predicted performance for these items. Together, these results suggest that the dlPFC is important for discrimination during elevated anxiety and that overgeneralization may reflect a deficit in dlPFC-mediated cognitive control.
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Andriotti T, Stavale R, Nafee T, Fakhry S, Mohamed MMA, Sofiyeva N, Ganho-Ávila A, Bogner A, Barbosa SP, Piton LS, Hirayama ALS, Gaccia G, Smith-Howard Junior TP, Miranda PC, Reyes KJC, Gragera A, Nishiwaki H, Boechat-Barros R. ASSERT trial - How to assess the safety and efficacy of a high frequency rTMS in postpartum depression ? A multicenter, double blinded, randomized, placebo-controlled clinical trial. Contemp Clin Trials Commun 2017; 5:86-91. [PMID: 29740625 PMCID: PMC5936708 DOI: 10.1016/j.conctc.2017.01.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Revised: 12/17/2016] [Accepted: 01/10/2017] [Indexed: 01/04/2023] Open
Abstract
Background Postpartum Depression affects a considerable number of women worldwide. This condition inflicts severe consequences to mother and child health. Thus far, available treatments have low response and high relapse rates. We designed this trial to evaluate a safe and more efficacious innovative therapy. Aims To report a feasible and ethical study design to assess the safety and efficacy of a high frequency repetitive Transcranial Magnetic Stimulation 10 Hz (rTMS) compared to sham rTMS in women with moderate to severe Post-Partum Depression using standard treatment (sertraline). To conduct an ancillary, exploratory, randomized, active controlled, double blind study with a hypothesis to assess the safety and efficacy of 10 Hz rTMS compared to sertraline. Methods A multicenter, parallel arm, randomized, placebo-controlled, double-blind design to assess safety and efficacy of 10 Hz rTMS compared to sham. An ancillary study will be conducted with parallel arm, randomized, active controlled and double dummy design to assess safety and efficacy of 10 Hz rTMS compared to sertraline.
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Affiliation(s)
- Tomas Andriotti
- Sao Camilo Hospital, Rua Dr. Plinio Barreto, 173, 174B, São Paulo, SP, 01313020, Brazil
| | - Rafaelly Stavale
- University of Brasilia, School of Health Sciences, Department of Nursing, Campus Universitario Darcy Ribeiro, Brasilia, DF, 70910-900, Brazil
| | - Tarek Nafee
- Beth Israel Deaconess Medical Center, Department of Cardiology, Perfuse Study Group, 330 Brookline Ave, Boston, MA, 02215, United States
| | - Stephanie Fakhry
- Iberoamerican University, School of Medicine, Av. Francia No. 129, Santo Domingo, DN, 10204, Dominican Republic
| | - Mahmoud M A Mohamed
- Umm Al-Quara University, Department of Clinical Pharmacy, Al Taif Road, Makkah, 24382, Saudi Arabia
| | - Nigar Sofiyeva
- Istanbul University, Cerrahpasa Medical Faculty, Department of Obstetrics and Gynecology, Cerrahpasa cad., Kocamustafapasa Mah., Faith, 34098, Istanbul, Turkey.,Yale University, School of Medicine, Department of Obstetrics and Gynecology, New Haven, 06510, Connecticut, USA
| | - Ana Ganho-Ávila
- Proaction Laboratory, Univeristy of Coimbra, Faculty of Psychology and Educational Sciences, Rua do Colegio Novo, 6153, 3001-802, Coimbra, Portugal.,Neuropsychophysiology Laboratory, University of Minho, Research Center in Psychology, Campus de Gualtar, 4710-057, Braga, Portugal
| | - Andreas Bogner
- Clinica of Visceral, Thoracic and Vascular Surgery, Technical University of Dresden, 01069, Dresden, Germany
| | - Sara P Barbosa
- University of São Paulo at Ribeirão Preto, College of Nursing, Av. dos Bandeirantes, 3900 Campus Universitário Ribeirão Preto, SP, 14040-902, Brazil
| | - Luciana S Piton
- Faculty of Medicine of ABC, Av. Príncipe de Galés, 821 - Vila Principe de Gales, Santo André, SP, 09060-650, Brazil
| | | | - Gisele Gaccia
- Univeristy of Mogi of Crosses, Av. Imperatriz Leopoldina, 550 - Vila Leopoldina, São Paulo, SP, 05305-000, Brazil
| | - Tomas P Smith-Howard Junior
- Metropolitan University of Santos, Campus Bandeirante I, Rua da Constituição no. 374, Vila Nova, Santos, SP, 11015-470, Brazil
| | - Priscila C Miranda
- University of Brasilia, Campus Universitario Darcy Ribeiro, Brasilia, DF, 70910-900, Brazil
| | - Karen J Campoverde Reyes
- Massachusetts General Hospital, Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, United States
| | - Alvaro Gragera
- University of Huelva Hospital Complex, Clinical Analysis Service, Ronda Exterior Nte, s/n, 21005, Huelva, Spain
| | - Hiroki Nishiwaki
- Center for Innovative Research for Communities and Clinical Excellence, Fukushima Medical University, 〒960-1295 Fukushima Prefecture, Fukushima, Hikarigaoka, Japan
| | - Raphael Boechat-Barros
- University of Brasilia, Psychiatric Department of Medicine School, Campus Universitario Darcy Ribeiro, Brasili, DF, 70910-900, Brazil
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D'Ostilio K, Garraux G. The Network Model of Depression as a Basis for New Therapeutic Strategies for Treating Major Depressive Disorder in Parkinson's Disease. Front Hum Neurosci 2016; 10:161. [PMID: 27148016 PMCID: PMC4840253 DOI: 10.3389/fnhum.2016.00161] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2015] [Accepted: 04/01/2016] [Indexed: 01/29/2023] Open
Abstract
The high prevalence of major depressive disorder in people with Parkinson’s disease (PD), its negative impact on health-related quality of life and the low response rate to conventional pharmacological therapies call to seek innovative treatments. Here, we review the new approaches for treating major depressive disorder in patients with PD within the framework of the network model of depression. According to this model, major depressive disorder reflects maladaptive neuronal plasticity. Non-invasive brain stimulation (NIBS) using high frequency repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex has been proposed as a feasible and effective strategy with minimal risk. The neurobiological basis of its therapeutic effect may involve neuroplastic modifications in limbic and cognitive networks. However, the way this networks reorganize might be strongly influenced by the environment. To address this issue, we propose a combined strategy that includes NIBS together with cognitive and behavioral interventions.
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Affiliation(s)
- Kevin D'Ostilio
- Movere Group, Cyclotron Research Center, University of Liege Liege, Belgium
| | - Gaëtan Garraux
- Movere Group, Cyclotron Research Center, University of LiegeLiege, Belgium; Department of Neurology, University Hospital CenterLiege, Belgium
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Etiévant A, Manta S, Latapy C, Magno LAV, Fecteau S, Beaulieu JM. Repetitive transcranial magnetic stimulation induces long-lasting changes in protein expression and histone acetylation. Sci Rep 2015; 5:16873. [PMID: 26585834 PMCID: PMC4653621 DOI: 10.1038/srep16873] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Accepted: 10/20/2015] [Indexed: 12/27/2022] Open
Abstract
The use of non-invasive brain stimulation like repetitive transcranial magnetic stimulation (rTMS) is an increasingly popular set of methods with promising results for the treatment of neurological and psychiatric disorders. Despite great enthusiasm, the impact of non-invasive brain stimulation on its neuronal substrates remains largely unknown. Here we show that rTMS applied over the frontal cortex of awaken mice induces dopamine D2 receptor dependent persistent changes of CDK5 and PSD-95 protein levels specifically within the stimulated brain area. Importantly, these modifications were associated with changes of histone acetylation at the promoter of these genes and prevented by administration of the histone deacetylase inhibitor MS-275. These findings show that, like several other psychoactive treatments, repeated rTMS sessions can exert long-lasting effects on neuronal substrates. This underscores the need of understanding these effects in the development of future clinical applications as well as in the establishment of improved guidelines to use rTMS in non-medical settings.
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Affiliation(s)
- Adeline Etiévant
- Department of psychiatry and neuroscience, Faculty of medicine, Université Laval. Québec City, Qc, Canada
| | - Stella Manta
- Department of psychiatry and neuroscience, Faculty of medicine, Université Laval. Québec City, Qc, Canada
| | - Camille Latapy
- Department of psychiatry and neuroscience, Faculty of medicine, Université Laval. Québec City, Qc, Canada
| | - Luiz Alexandre V Magno
- Department of psychiatry and neuroscience, Faculty of medicine, Université Laval. Québec City, Qc, Canada.,Universidade Federal de Minas Gerai, Belo Horizonte, Brazil
| | - Shirley Fecteau
- Departement of readaptation, Faculty of medicine, Université Laval, Québec City, Qc, Canada and Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Jean-Martin Beaulieu
- Department of psychiatry and neuroscience, Faculty of medicine, Université Laval. Québec City, Qc, Canada
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Garcia G, Norise C, Faseyitan O, Naeser MA, Hamilton RH. Utilizing repetitive transcranial magnetic stimulation to improve language function in stroke patients with chronic non-fluent aphasia. J Vis Exp 2013:e50228. [PMID: 23852365 DOI: 10.3791/50228] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
Transcranial magnetic stimulation (TMS) has been shown to significantly improve language function in patients with non-fluent aphasia(1). In this experiment, we demonstrate the administration of low-frequency repetitive TMS (rTMS) to an optimal stimulation site in the right hemisphere in patients with chronic non-fluent aphasia. A battery of standardized language measures is administered in order to assess baseline performance. Patients are subsequently randomized to either receive real rTMS or initial sham stimulation. Patients in the real stimulation undergo a site-finding phase, comprised of a series of six rTMS sessions administered over five days; stimulation is delivered to a different site in the right frontal lobe during each of these sessions. Each site-finding session consists of 600 pulses of 1 Hz rTMS, preceded and followed by a picture-naming task. By comparing the degree of transient change in naming ability elicited by stimulation of candidate sites, we are able to locate the area of optimal response for each individual patient. We then administer rTMS to this site during the treatment phase. During treatment, patients undergo a total of ten days of stimulation over the span of two weeks; each session is comprised of 20 min of 1 Hz rTMS delivered at 90% resting motor threshold. Stimulation is paired with an fMRI-naming task on the first and last days of treatment. After the treatment phase is complete, the language battery obtained at baseline is repeated two and six months following stimulation in order to identify rTMS-induced changes in performance. The fMRI-naming task is also repeated two and six months following treatment. Patients who are randomized to the sham arm of the study undergo sham site-finding, sham treatment, fMRI-naming studies, and repeat language testing two months after completing sham treatment. Sham patients then cross over into the real stimulation arm, completing real site-finding, real treatment, fMRI, and two- and six-month post-stimulation language testing.
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Affiliation(s)
- Gabriella Garcia
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania
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Breden Crouse EL. Transcranial magnetic stimulation for major depressive disorder: What a pharmacist should know. Ment Health Clin 2012. [DOI: 10.9740/mhc.n129615] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Transcranial magnetic stimulation utilizes strong pulsed magnetic fields from an insulated coil which generate electrical currents resulting in neuronal depolarization in the cortex. Currently, the user manual only cautions against the use of tricyclic antidepressants, antipsychotics, and other medications that lower the seizure threshold during TMS therapy. However, post-marketing reports suggest caution should also be utilized when combining TMS with other antidepressants (e.g. bupropion, serotonin reuptake inhibitors) and stimulants. Data show efficacy of approximately 30%. Adverse effects more commonly reported include application site pain (35.8%), muscle twitching (20.6%), application site discomfort (10.9%), skin pain (8.5%), toothache (7.3%), facial pain (6.7%), and eye pain (6.1%).
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Affiliation(s)
- Ericka L. Breden Crouse
- 1Clinical Pharmacy Specialist, Psychiatry, Virginia Commonwealth University Health System, Richmond, VA
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