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Shahabi MS, Shalbaf A, Rostami R, Kazemi R. Brain stimulation outcome prediction in Major Depressive Disorder by deep learning models using EEG representations. Comput Methods Biomech Biomed Engin 2025:1-14. [PMID: 40434017 DOI: 10.1080/10255842.2025.2511222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2024] [Revised: 03/06/2025] [Accepted: 05/19/2025] [Indexed: 05/29/2025]
Abstract
Major Depressive Disorder (MDD) is known as a widespread illness and needs a timely treatment. The treatment procedure is currently based on the trial and error between various treatments. An individualized treatment selection is crucial for saving time and financial resources and preventing possible side effects. Because of the complex nature of this problem, a Deep Learning (DL) approach, as a promising method for the precision medicine, was utilized to identify the responders to the treatment using pre-treatment EEG signals. Eighty-three patients with MDD participated in this study to receive treatment using Repetitive Transcranial Magnetic Stimulation (rTMS). A deep hybrid neural network was developed based on three pre-trained convolutional neural networks named DenseNet121, EfficientNetB0, and Xception. The training of each model was performed by feeding three types of EEG representations as the inputs into the models including the Wavelet Transform (WT) images, the connectivity matrix between electrode pairs, and the raw EEG signals. The performance of the proposed models were assessed for the three different input types and achieved the highest accuracy of 94.7% in classifying patients as responders or non-responders when utilizing a sequence of raw EEG images. For the WT and connectivity inputs the best accuracy of model was 94.38% and 94.25% respectively. Therefore, the proposed model can be a step forward towards the clinical implementation of an end-to-end treatment selection framework using raw EEG signals.
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Affiliation(s)
- Mohsen Sadat Shahabi
- Department of Biomedical Engineering and Medical Physics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ahmad Shalbaf
- Department of Biomedical Engineering and Medical Physics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Reza Rostami
- Department of Psychology, University of Tehran, Tehran, Iran
| | - Reza Kazemi
- Faculty of Entrepreneurship, University of Tehran, Tehran, Iran
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Saha C, Figley CR, Lithgow B, Fitzgerald PB, Koski L, Mansouri B, Anssari N, Wang X, Moussavi Z. Can Brain Volume-Driven Characteristic Features Predict the Response of Alzheimer's Patients to Repetitive Transcranial Magnetic Stimulation? A Pilot Study. Brain Sci 2024; 14:226. [PMID: 38539615 PMCID: PMC10968477 DOI: 10.3390/brainsci14030226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 02/20/2024] [Accepted: 02/25/2024] [Indexed: 11/11/2024] Open
Abstract
This study is a post-hoc examination of baseline MRI data from a clinical trial investigating the efficacy of repetitive transcranial magnetic stimulation (rTMS) as a treatment for patients with mild-moderate Alzheimer's disease (AD). Herein, we investigated whether the analysis of baseline MRI data could predict the response of patients to rTMS treatment. Whole-brain T1-weighted MRI scans of 75 participants collected at baseline were analyzed. The analyses were run on the gray matter (GM) and white matter (WM) of the left and right dorsolateral prefrontal cortex (DLPFC), as that was the rTMS application site. The primary outcome measure was the Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog). The response to treatment was determined based on ADAS-Cog scores and secondary outcome measures. The analysis of covariance showed that responders to active treatment had a significantly lower baseline GM volume in the right DLPFC and a higher GM asymmetry index in the DLPFC region compared to those in non-responders. Logistic regression with a repeated five-fold cross-validated analysis using the MRI-driven features of the initial 75 participants provided a mean accuracy of 0.69 and an area under the receiver operating characteristic curve of 0.74 for separating responders and non-responders. The results suggest that GM volume or asymmetry in the target area of active rTMS treatment (DLPFC region in this study) may be a weak predictor of rTMS treatment efficacy. These results need more data to draw more robust conclusions.
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Affiliation(s)
- Chandan Saha
- Biomedical Engineering Program, University of Manitoba, Winnipeg, MB R3T 5V6, Canada
| | - Chase R. Figley
- Department of Radiology, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
| | - Brian Lithgow
- Biomedical Engineering Program, University of Manitoba, Winnipeg, MB R3T 5V6, Canada
- Department of Psychiatry (MAPRC), Monash University, Melbourne VIC 3004, Australia
| | - Paul B. Fitzgerald
- Department of Psychiatry (MAPRC), Monash University, Melbourne VIC 3004, Australia
| | - Lisa Koski
- Department of Psychology, Faculty of Science, McGill University, Montreal, QC H3A 1G1, Canada
| | - Behzad Mansouri
- Brain, Vision and Concussion Clinic-iScope, Winnipeg, MB R2M 2X9, Canada
| | - Neda Anssari
- Brain, Vision and Concussion Clinic-iScope, Winnipeg, MB R2M 2X9, Canada
| | - Xikui Wang
- Warren Center for Actuarial Studies and Research, University of Manitoba, Winnipeg, MB R3T 5V4, Canada
| | - Zahra Moussavi
- Biomedical Engineering Program, University of Manitoba, Winnipeg, MB R3T 5V6, Canada
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Wei L, Zhang Y, Wang J, Xu L, Yang K, Lv X, Zhu Z, Gong Q, Hu W, Li X, Qian M, Shen Y, Chen W. Parietal-hippocampal rTMS improves cognitive function in Alzheimer's disease and increases dynamic functional connectivity of default mode network. Psychiatry Res 2022; 315:114721. [PMID: 35839637 DOI: 10.1016/j.psychres.2022.114721] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 07/06/2022] [Accepted: 07/07/2022] [Indexed: 11/26/2022]
Abstract
Parietal-hippocampal repetitive transcranial magnetic stimulation (rTMS) improves cognitive function in Alzheimer's disease (AD), however, the underlying therapeutic mechanism has not been elucidated. A double-blind, randomized, sham-controlled parietal-hippocampal rTMS trial (five sessions/week for a total of 10 sessions) of mild-to-moderate AD patients was conducted in the study. High-frequency rTMS was applied to a subject-specific left lateral parietal region with the highest functional connectivity with the hippocampus based on resting-state fMRI. A multimodal MRI scan and a complete neuropsychological battery of tests were conducted at baseline, immediately after the intervention and 12-week follow-up after the rTMS treatment. Compared to sham treatment (n = 27), patients undergoing active rTMS treatment (n = 29) showed higher Mini Mental State Examination (MMSE) score and dynamic functional connectivity (dFC) magnitude of the default mode network (DMN) after two weeks of rTMS treatment, but not at 12-week follow-up. A significant positive correlation was observed between changes in MMSE and changes in the dFC magnitude of DMN in patients who underwent active-rTMS treatment, but not in those who received sham-rTMS treatment. The findings of the current study indicate that fMRI-guided rTMS treatment improves cognitive function of AD patients in the short term, and DMN functional connectivity contributes to therapeutic effectiveness of rTMS.
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Affiliation(s)
- Lili Wei
- Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, East Qingchun Road 3#, Hangzhou, Zhejiang 310016, China
| | - Yingchun Zhang
- Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, East Qingchun Road 3#, Hangzhou, Zhejiang 310016, China
| | - Jintao Wang
- Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, East Qingchun Road 3#, Hangzhou, Zhejiang 310016, China
| | - Luoyi Xu
- Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, East Qingchun Road 3#, Hangzhou, Zhejiang 310016, China
| | - Kehua Yang
- Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, East Qingchun Road 3#, Hangzhou, Zhejiang 310016, China
| | - Xinghui Lv
- Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, East Qingchun Road 3#, Hangzhou, Zhejiang 310016, China
| | - Zhenwei Zhu
- Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, East Qingchun Road 3#, Hangzhou, Zhejiang 310016, China
| | - Qian Gong
- Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, East Qingchun Road 3#, Hangzhou, Zhejiang 310016, China
| | - Weiming Hu
- Third People's Hospital of Quzhou, Quzhou, Zhejiang 324003, China
| | - Xia Li
- Shanghai Mental Health Center, Shanghai 200030, China
| | - Mincai Qian
- Third People's Hospital of Huzhou, Huzhou, Zhejiang 313002, China.
| | - Yuedi Shen
- Hangzhou Normal University School of Medicine, Hangzhou, Zhejiang 311121, China.
| | - Wei Chen
- Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, East Qingchun Road 3#, Hangzhou, Zhejiang 310016, China; Department of Psychology and Behavioral Sciences, Zhejiang University, Hangzhou 310007, China; Key Laboratory of Medical Neurobiology of Zhejiang Province, Hangzhou 310016, China.
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Lithgow BJ, Dastgheib Z, Moussavi Z. Baseline Prediction of rTMS efficacy in Alzheimer patients. Psychiatry Res 2022; 308:114348. [PMID: 34952254 DOI: 10.1016/j.psychres.2021.114348] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 12/13/2021] [Accepted: 12/16/2021] [Indexed: 10/19/2022]
Abstract
Repetitive transcranial magnetic stimulation (rTMS) with extensive 2-6-week protocols are applied to improve cognition and/or slow the cognitive decline seen in Alzheimer's Disease (AD). To date, there are no means to predict the response of a patient to rTMS treatment at baseline. Electrovestibulography (EVestG) biomarkers can be used to predict, at baseline, the efficacy of rTMS when applied to AD individuals. In a population of 27 AD patients (8 with significant cerebrovascular symptomatology, labelled ADcvd) EVestG signals were measured before and after rTMS treatment, and then compared with 16 age-matched healthy controls. MoCA was measured at baseline, whilst ADAS-Cog was the primary outcome measure. AD severity and comorbid cerebrovascular disease were treated as covariates. Using ADAS-Cog total score change, 13/27 AD/ADcvd patients improved with rTMS and 14/27 showed no-improvement. Leave-one-out-cross-validated linear-discriminant-analysis using two EVestG features yielded a blind accuracy of 75% for separating the improved and non-improved populations. Three-way separation of improved/non-improved/control accuracy was 91.9% using MoCA (67% alone) and one EVestG feature (66% alone). AD severity affects the rTMS treatment efficacy. The effect of existing significant cerebrovascular symptomatology on the efficacy of rTMS treatment remains unresolved. Baseline EVestG features can be predictive of the efficacy of rTMS treatment.
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Affiliation(s)
- Brian J Lithgow
- Diagnostic and Neurosignal Processing Research Laboratory, Biomedical Engineering Program, University of Manitoba, Riverview Health Centre, Manitoba, Canada; Monash Alfred Psychiatry Research Centre, Victoria, Australia.
| | - Zeinab Dastgheib
- Diagnostic and Neurosignal Processing Research Laboratory, Biomedical Engineering Program, University of Manitoba, Riverview Health Centre, Manitoba, Canada
| | - Zahra Moussavi
- Diagnostic and Neurosignal Processing Research Laboratory, Biomedical Engineering Program, University of Manitoba, Riverview Health Centre, Manitoba, Canada
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Teti Mayer J, Masse C, Chopard G, Nicolier M, Bereau M, Magnin E, Monnin J, Tio G, Haffen E, Vandel P, Bennabi D. Repetitive Transcranial Magnetic Stimulation as an Add-On Treatment for Cognitive Impairment in Alzheimer's Disease and Its Impact on Self-Rated Quality of Life and Caregiver's Burden. Brain Sci 2021; 11:brainsci11060740. [PMID: 34204860 PMCID: PMC8227849 DOI: 10.3390/brainsci11060740] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 05/21/2021] [Accepted: 05/22/2021] [Indexed: 01/10/2023] Open
Abstract
Alzheimer’s disease (AD) is associated with progressive memory loss and decline in executive functions, as well as neuropsychiatric symptoms. Patients usually consider quality of life (QoL) and mood as more important for their health status than disease-specific physical and mental symptoms. In this open-label uncontrolled trial, 12 subjects diagnosed with AD underwent 10 sessions of repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (10 Hz, 20 min, 2000 pulses/day, 110% MT). Outcomes were measured before and 30 days after treatment. Our primary objective was to test the efficacy of rTMS as an add-on treatment for AD on the global cognitive function, assessed through the Mini-Mental State Examination (MMSE) and the Mattis Dementia Rating Scale (MDRS). As secondary objectives, the detailed effect on cognitive functions, depression and anxiety symptoms, QoL, and functionality in daily life activities were evaluated, as well as correlations between QoL and cognition, depression and anxiety scores. The treatment significantly enhanced semantic memory and reduced anxiety. Improvement of these features in AD could become an important target for treatment strategies. Although limited by its design, this trial may contribute with another perspective on the analysis and the impact of rTMS on AD.
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Affiliation(s)
- Juliana Teti Mayer
- Laboratoire de Recherches Intégratives en Neurosciences et Psychologie Cognitive, Université Bourgogne Franche-Comté, 25000 Besançon, France; (C.M.); (G.C.); (M.N.); (M.B.); (E.M.); (J.M.); (E.H.); (P.V.); (D.B.)
- Service de Psychiatrie de l’Adulte, Centre Hospitalier Universitaire de Besançon, CEDEX, 25030 Besançon, France;
- Correspondence:
| | - Caroline Masse
- Laboratoire de Recherches Intégratives en Neurosciences et Psychologie Cognitive, Université Bourgogne Franche-Comté, 25000 Besançon, France; (C.M.); (G.C.); (M.N.); (M.B.); (E.M.); (J.M.); (E.H.); (P.V.); (D.B.)
- Service de Psychiatrie de l’Adulte, Centre Hospitalier Universitaire de Besançon, CEDEX, 25030 Besançon, France;
| | - Gilles Chopard
- Laboratoire de Recherches Intégratives en Neurosciences et Psychologie Cognitive, Université Bourgogne Franche-Comté, 25000 Besançon, France; (C.M.); (G.C.); (M.N.); (M.B.); (E.M.); (J.M.); (E.H.); (P.V.); (D.B.)
- Service de Psychiatrie de l’Adulte, Centre Hospitalier Universitaire de Besançon, CEDEX, 25030 Besançon, France;
- Service de Neurologie, Centre Hospitalier Universitaire de Besançon, CEDEX, 25030 Besançon, France
- Centre Mémoire Ressources et Recherche, Centre Hospitalier Universitaire de Besançon, CEDEX, 25030 Besançon, France
| | - Magali Nicolier
- Laboratoire de Recherches Intégratives en Neurosciences et Psychologie Cognitive, Université Bourgogne Franche-Comté, 25000 Besançon, France; (C.M.); (G.C.); (M.N.); (M.B.); (E.M.); (J.M.); (E.H.); (P.V.); (D.B.)
- Service de Psychiatrie de l’Adulte, Centre Hospitalier Universitaire de Besançon, CEDEX, 25030 Besançon, France;
- Centre d’Investigation Clinique, INSERM CIC 1431, Centre Hospitalier Universitaire de Besançon, CEDEX, 25030 Besançon, France
| | - Matthieu Bereau
- Laboratoire de Recherches Intégratives en Neurosciences et Psychologie Cognitive, Université Bourgogne Franche-Comté, 25000 Besançon, France; (C.M.); (G.C.); (M.N.); (M.B.); (E.M.); (J.M.); (E.H.); (P.V.); (D.B.)
- Service de Neurologie, Centre Hospitalier Universitaire de Besançon, CEDEX, 25030 Besançon, France
| | - Eloi Magnin
- Laboratoire de Recherches Intégratives en Neurosciences et Psychologie Cognitive, Université Bourgogne Franche-Comté, 25000 Besançon, France; (C.M.); (G.C.); (M.N.); (M.B.); (E.M.); (J.M.); (E.H.); (P.V.); (D.B.)
- Service de Neurologie, Centre Hospitalier Universitaire de Besançon, CEDEX, 25030 Besançon, France
| | - Julie Monnin
- Laboratoire de Recherches Intégratives en Neurosciences et Psychologie Cognitive, Université Bourgogne Franche-Comté, 25000 Besançon, France; (C.M.); (G.C.); (M.N.); (M.B.); (E.M.); (J.M.); (E.H.); (P.V.); (D.B.)
- Service de Psychiatrie de l’Adulte, Centre Hospitalier Universitaire de Besançon, CEDEX, 25030 Besançon, France;
| | - Gregory Tio
- Service de Psychiatrie de l’Adulte, Centre Hospitalier Universitaire de Besançon, CEDEX, 25030 Besançon, France;
- Centre d’Investigation Clinique, INSERM CIC 1431, Centre Hospitalier Universitaire de Besançon, CEDEX, 25030 Besançon, France
| | - Emmanuel Haffen
- Laboratoire de Recherches Intégratives en Neurosciences et Psychologie Cognitive, Université Bourgogne Franche-Comté, 25000 Besançon, France; (C.M.); (G.C.); (M.N.); (M.B.); (E.M.); (J.M.); (E.H.); (P.V.); (D.B.)
- Service de Psychiatrie de l’Adulte, Centre Hospitalier Universitaire de Besançon, CEDEX, 25030 Besançon, France;
- Centre d’Investigation Clinique, INSERM CIC 1431, Centre Hospitalier Universitaire de Besançon, CEDEX, 25030 Besançon, France
- Centre Expert Dépression Résistante FondaMental, Centre Hospitalier Universitaire de Besançon, CEDEX, 25030 Besançon, France
| | - Pierre Vandel
- Laboratoire de Recherches Intégratives en Neurosciences et Psychologie Cognitive, Université Bourgogne Franche-Comté, 25000 Besançon, France; (C.M.); (G.C.); (M.N.); (M.B.); (E.M.); (J.M.); (E.H.); (P.V.); (D.B.)
- Service de Psychiatrie de l’Adulte, Centre Hospitalier Universitaire de Besançon, CEDEX, 25030 Besançon, France;
- Centre Mémoire Ressources et Recherche, Centre Hospitalier Universitaire de Besançon, CEDEX, 25030 Besançon, France
| | - Djamila Bennabi
- Laboratoire de Recherches Intégratives en Neurosciences et Psychologie Cognitive, Université Bourgogne Franche-Comté, 25000 Besançon, France; (C.M.); (G.C.); (M.N.); (M.B.); (E.M.); (J.M.); (E.H.); (P.V.); (D.B.)
- Service de Psychiatrie de l’Adulte, Centre Hospitalier Universitaire de Besançon, CEDEX, 25030 Besançon, France;
- Centre d’Investigation Clinique, INSERM CIC 1431, Centre Hospitalier Universitaire de Besançon, CEDEX, 25030 Besançon, France
- Centre Expert Dépression Résistante FondaMental, Centre Hospitalier Universitaire de Besançon, CEDEX, 25030 Besançon, France
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Moussavi Z, Rutherford G, Lithgow B, Millikin C, Modirrousta M, Mansouri B, Wang X, Omelan C, Fellows L, Fitzgerald P, Koski L. Repeated Transcranial Magnetic Stimulation for Improving Cognition in Patients With Alzheimer Disease: Protocol for a Randomized, Double-Blind, Placebo-Controlled Trial. JMIR Res Protoc 2021; 10:e25144. [PMID: 33416500 PMCID: PMC7822717 DOI: 10.2196/25144] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 11/06/2020] [Accepted: 11/24/2020] [Indexed: 12/22/2022] Open
Abstract
Background Alzheimer disease has no known cure. As existing pharmacologic interventions only modestly slow cognitive decline, there is a need for new treatments. Recent trials of repetitive transcranial magnetic stimulation (rTMS) have reported encouraging results for improving or stabilizing cognition in patients diagnosed with Alzheimer dementia. However, owing to small samples and lack of a well-controlled double-blind design, the results to date are inconclusive. This paper presents the protocol for a large placebo-controlled double-blind study designed with sufficient statistical rigor to measure the efficacy of rTMS treatment in patients with Alzheimer dementia. Objective The objectives are to (1) recruit and enroll up to 200 eligible participants, (2) estimate the difference in treatment effects between active treatment and sham treatment, (3) estimate the difference in treatment effects between two doses of rTMS applications, (4) estimate the duration of treatment effects among responders to active rTMS treatment, and (5) estimate the effect of dementia severity on treatment outcomes among patients receiving active rTMS treatment. Methods We have designed our study to be a double-blind, randomized, placebo-controlled clinical trial investigating the short- and long-term (up to 6 months) benefits of active rTMS treatment at two doses (10 sessions over 2 weeks and 20 sessions over 4 weeks) compared with sham rTMS treatment. The study will include patients aged ≥55 years who are diagnosed with Alzheimer disease at an early to moderate stage and have no history of seizures and no major depression. The primary outcome measure is the change in the Alzheimer Disease Assessment Scale-Cognitive Subscale score from pretreatment to posttreatment. Secondary outcomes are changes in performance on tests of frontal lobe functioning (Stroop test and verbal fluency), changes in neuropsychiatric symptoms (Neuropsychiatric Inventory Questionnaire), and changes in activities of daily living (Alzheimer Disease Co-operative Study-Activities of Daily Living Inventory). Tolerability of the intervention will be assessed using a modification of the Treatment Satisfaction Questionnaire for Medication. We assess participants at baseline and 3, 5, 8, 16, and 24 weeks after the intervention. Results As of November 1, 2020, we have screened 523 individuals, out of which 133 were eligible and have been enrolled. Out of the 133 individuals, 104 have completed the study. Moreover, as of November 1, 2020, there has been no serious adverse event. We anticipate that rTMS will considerably improve cognitive function, with effects lasting up to 3 months. Moreover, we expect rTMS to be a well-tolerated treatment with no serious side effect. Conclusions This protocol design will allow to address both the rTMS active treatment dose and its short- and long-term effects compared with sham treatment in large samples. Trial Registration ClinicalTrials.gov NCT02908815; https://clinicaltrials.gov/ct2/show/NCT02908815 International Registered Report Identifier (IRRID) DERR1-10.2196/25144
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Affiliation(s)
- Zahra Moussavi
- Biomedical Engineering Program, The University of Manitoba, Winnipeg, MB, Canada
| | - Grant Rutherford
- Biomedical Engineering Program, The University of Manitoba, Winnipeg, MB, Canada
| | - Brian Lithgow
- Biomedical Engineering Program, The University of Manitoba, Winnipeg, MB, Canada
| | - Colleen Millikin
- Department of Clinical Health Psychology, Max Rady College of Medicine, The University of Manitoba, Winnipeg, MB, Canada
| | - Mandana Modirrousta
- Department of Psychiatry, Max Rady College of Medicine, The University of Manitoba, Winnipeg, MB, Canada
| | | | - Xikui Wang
- Warren Centre for Actuarial Studies and Research, I H Asper School of Business, The University of Manitoba, Winnipeg, MB, Canada
| | - Craig Omelan
- Department of Psychiatry, Max Rady College of Medicine, The University of Manitoba, Winnipeg, MB, Canada
| | - Lesley Fellows
- Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada
| | - Paul Fitzgerald
- Department of Psychiatry, Monash University, Melbourne, Australia
| | - Lisa Koski
- Department of Psychology, Faculty of Science, McGill University, Montreal, QC, Canada
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Thomson AC, Sack AT. How to Design Optimal Accelerated rTMS Protocols Capable of Promoting Therapeutically Beneficial Metaplasticity. Front Neurol 2020; 11:599918. [PMID: 33224103 PMCID: PMC7674552 DOI: 10.3389/fneur.2020.599918] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Accepted: 10/22/2020] [Indexed: 12/11/2022] Open
Affiliation(s)
- Alix C Thomson
- Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands.,Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht, Netherlands.,Centre for Integrative Neuroscience, Faculty of Psychology and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands
| | - Alexander T Sack
- Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands.,Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht, Netherlands.,Centre for Integrative Neuroscience, Faculty of Psychology and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands
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Wang H, Jin J, Cui D, Wang X, Li Y, Liu Z, Yin T. Cortico-Hippocampal Brain Connectivity-Guided Repetitive Transcranial Magnetic Stimulation Enhances Face-Cued Word-Based Associative Memory in the Short Term. Front Hum Neurosci 2020; 14:541791. [PMID: 33192388 PMCID: PMC7662091 DOI: 10.3389/fnhum.2020.541791] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 09/25/2020] [Indexed: 11/13/2022] Open
Abstract
Repetitive transcranial magnetic stimulation (rTMS) can be used to enhance the associative memory of healthy subjects and patients with Alzheimer's disease (AD). However, the question of where the stimulation should be applied is still unresolved. In a preliminary survey for an effective and feasible solution to this problem, we identified three representative rTMS targets using cortico-hippocampal connectivity, calculated using resting-state fMRI (rs-fMRI) data from 80 young, healthy subjects: (1) the cortical area with the strongest connectivity across the whole cerebral cortical area; (2) the whole lateral parietal cortical area; and (3) the whole medial prefrontal cortical area. We then compared the short-term effects on associative memory, which was tested using face-cued word recall by applying rTMS to three identified targets in a single population of eight healthy adults. Each treatment lasted for 2 days. Associative memory performance was measured at four time points: before and after stimulation on the first day (baseline and post 1) and before and after stimulation on the second day (post 2 and post 3). Compared with baseline levels, 20 min of high-frequency rTMS delivered to target 2 or target 3 produced a significant increase in the mean accuracy of associative memory performance at the post 3 time point alone (target 2, P = 0.0035; target 3, P = 0.0012). Compared with the sham conditions, significant increases in the mean associative memory performance were observed when high-frequency rTMS was delivered to target 2 (P = 0.02) and target 3 (P = 0.012), but not when delivered to target 1 (P = 0.1). Compared with baseline levels, 20 min of high-frequency rTMS delivered to target 3 produced a significant reduction in the mean reaction time of associative memory only at time points post 1 (P = 0.0464) and post 3 (P = 0.0477). Compared with the sham conditions, significant reductions in the mean reaction time of associative memory were observed when high-frequency rTMS was delivered to target 3 (P = 0.006), but not when delivered to target 1 (P = 0.471) or target 2 (P = 0.365). Our findings indicate that stimulation of the locations with the strongest cortico-hippocampal connectivity within the lateral parietal cortical or medial prefrontal cortical areas is effective in enhancing face-word recall-based associative memory in the short term.
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Affiliation(s)
- He Wang
- Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China
| | - Jingna Jin
- Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China
| | - Dong Cui
- Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China
| | - Xin Wang
- Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China
| | - Ying Li
- Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China
| | - Zhipeng Liu
- Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China
| | - Tao Yin
- Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China
- Neuroscience Center, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
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9
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Weiler M, Stieger KC, Long JM, Rapp PR. Transcranial Magnetic Stimulation in Alzheimer's Disease: Are We Ready? eNeuro 2020; 7:ENEURO.0235-19.2019. [PMID: 31848209 PMCID: PMC6948923 DOI: 10.1523/eneuro.0235-19.2019] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 12/09/2019] [Accepted: 12/11/2019] [Indexed: 02/08/2023] Open
Abstract
Transcranial magnetic stimulation (TMS) is among a growing family of noninvasive brain stimulation techniques being developed to treat multiple neurocognitive disorders, including Alzheimer's disease (AD). Although small clinical trials in AD have reported positive effects on cognitive outcome measures, significant knowledge gaps remain, and little attention has been directed at examining the potential influence of TMS on AD pathogenesis. Our review briefly outlines some of the proposed neurobiological mechanisms of TMS benefits in AD, with particular emphasis on the modulatory effects on excitatory/inhibitory balance. On the basis of converging evidence from multiple fields, we caution that TMS therapeutic protocols established in young adults may have unexpected detrimental effects in older individuals or in the brain compromised by AD pathology. Our review surveys clinical studies of TMS in AD alongside basic research as a guide for moving this important area of work forward toward effective treatment development.
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Affiliation(s)
- Marina Weiler
- Neurocognitive Aging Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, Intramural Research Program, Baltimore, Maryland 21224
| | - Kevin C Stieger
- Neurocognitive Aging Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, Intramural Research Program, Baltimore, Maryland 21224
| | - Jeffrey M Long
- Neurocognitive Aging Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, Intramural Research Program, Baltimore, Maryland 21224
| | - Peter R Rapp
- Neurocognitive Aging Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, Intramural Research Program, Baltimore, Maryland 21224
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10
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Moussavi Z, Suleiman A, Rutherford G, Ranjbar Pouya O, Dastgheib Z, Zhang W, Salter J, Wang X, Mansouri B, Lithgow B. A Pilot Randomised Double-Blind Study of the Tolerability and efficacy of repetitive Transcranial Magnetic Stimulation on Persistent Post-Concussion Syndrome. Sci Rep 2019; 9:5498. [PMID: 30940870 PMCID: PMC6445141 DOI: 10.1038/s41598-019-41923-6] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Accepted: 03/19/2019] [Indexed: 12/13/2022] Open
Abstract
This study investigates the effect of Repetitive Transcranial Magnetic Stimulation (rTMS) on persistent post-concussion syndrome (PCS). The study design was a randomized (coin toss), placebo controlled, and double-blind study. Thirty-seven participants with PCS were assessed for eligibility; 22 were randomised and 18 completed the study requirements. Half the participants with PCS were given an Active rTMS intervention and the other half given Sham rTMS over 3 weeks. Follow ups were at the end of treatment and at 30 and 60 days. The primary outcome measure was the Rivermead Post-Concussion Symptoms Questionnaire (RPQ3 & RPQ13). The results indicate participants with more recent injuries (<12 month), who received Active rTMS, showed significant improvements compared to those of: 1) the same subgroup who received Sham, and 2) those with a longer duration of injury (>14 months) who received Active rTMS. This improvement predominantly manifested in RPQ13 in the follow up periods 1 and 2 months after the intervention (RPQ13 change (mean ± SD): at 1 month, Active = −21.8 ± 6.6, Sham = −2.2 ± 9.8; at 2 months, Active = −21.2 ± 5.3, Sham = −5.4 ± 13.7). No improvement was found in the subgroup with longer duration injuries. The results support rTMS as a tolerable and potentially effective treatment option for individuals with a recent (<1 year) concussion.
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Affiliation(s)
- Zahra Moussavi
- Biomedical Engineering, University of Manitoba, Winnipeg, Canada. .,Riverview Health Centre, Winnipeg, Canada.
| | | | - Grant Rutherford
- Biomedical Engineering, University of Manitoba, Winnipeg, Canada
| | | | - Zeinab Dastgheib
- Biomedical Engineering, University of Manitoba, Winnipeg, Canada
| | - Weijia Zhang
- Statistics Department, University of Manitoba, Winnipeg, Canada
| | | | - Xikui Wang
- Statistics Department, University of Manitoba, Winnipeg, Canada
| | - Behzad Mansouri
- Biomedical Engineering, University of Manitoba, Winnipeg, Canada.,Neurology Department, University of Manitoba, Winnipeg, Canada
| | - Brian Lithgow
- Biomedical Engineering, University of Manitoba, Winnipeg, Canada.,Riverview Health Centre, Winnipeg, Canada.,Monash Alfred Psychiatry Research Center, Melbourne, Australia
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11
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Effects of Repetitive Transcranial Magnetic Stimulation over Prefrontal Cortex on Attention in Psychiatric Disorders: A Systematic Review. J Clin Med 2019; 8:jcm8040416. [PMID: 30934685 PMCID: PMC6518000 DOI: 10.3390/jcm8040416] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Revised: 03/10/2019] [Accepted: 03/19/2019] [Indexed: 01/20/2023] Open
Abstract
Repetitive transcranial magnetic stimulation (rTMS) may be effective for enhancing cognitive functioning. In this review, we aimed to systematically evaluate the effects of rTMS on attention in psychiatric diseases. In particular, we searched PubMed and Embase to examine the effectiveness of rTMS administered to the dorsolateral prefrontal cortex (DLPFC) on this specific cognitive domain. The search identified 24 articles, 21 of which met inclusion and exclusion criteria. Among them, nine were conducted in patients with depression, four in patients with schizophrenia, three in patients with autism spectrum disorder (ASD), two in patients with attention deficit hyperactivity disorder, one each in patients with Alzheimer's disease and in patients with alcohol or methamphetamine addiction. No evidence for cognitive adverse effects was found in all the included rTMS studies. Several studies showed a significant improvement of attentional function in patients with depression and schizophrenia. The beneficial effects on attention and other executive functions suggest that rTMS has the potential to target core features of ASD. rTMS may influence the attentional networks in alcohol-dependent and other addicted patients. We also reviewed and discussed the studies assessing the effects of rTMS on attention in the healthy population. This review suggests that prefrontal rTMS could exert procognitive effects on attention in patients with many psychiatric disorders.
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12
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Heath A, Taylor JL, McNerney MW. rTMS for the treatment of Alzheimer's disease: where should we be stimulating? Expert Rev Neurother 2018; 18:903-905. [PMID: 30350733 DOI: 10.1080/14737175.2018.1538792] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Affiliation(s)
- Alesha Heath
- a Experimental and Regenerative Neurosciences , University of Western Australia , Crawley , Australia.,b Perron Institute for Neurological and Translational Science , Nedlands , Australia
| | - J L Taylor
- c Department of Veterans Affairs Palo Alto Health Care System , Sierra Pacific MIRECC , Palo Alto , USA.,d Department of Psychiatry and Behavioral Studies , Stanford University School of Medecine , Palo Alto , USA
| | - M Windy McNerney
- c Department of Veterans Affairs Palo Alto Health Care System , Sierra Pacific MIRECC , Palo Alto , USA.,d Department of Psychiatry and Behavioral Studies , Stanford University School of Medecine , Palo Alto , USA
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13
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Sabesan P, Lankappa S, Khalifa N, Krishnan V, Gandhi R, Palaniyappan L. Transcranial magnetic stimulation for geriatric depression: Promises and pitfalls. World J Psychiatry 2015; 5:170-181. [PMID: 26110119 PMCID: PMC4473489 DOI: 10.5498/wjp.v5.i2.170] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2014] [Revised: 03/04/2015] [Accepted: 04/14/2015] [Indexed: 02/05/2023] Open
Abstract
As the global population gets older, depression in the elderly is emerging as an important health issue. A major challenge in treating geriatric depression is the lack of robust efficacy for many treatments that are of significant benefit to depressed working age adults. Repetitive transcranial magnetic stimulation (rTMS) is a novel physical treatment approach used mostly in working age adults with depression. Many TMS trials and clinics continue to exclude the elderly from treatment citing lack of evidence in this age group. In this review, we appraise the evidence regarding the safety and efficacy of rTMS in the elderly. A consistent observation supporting a high degree of tolerability and safety among the elderly patients emerged across the Randomised Controlled Trials and the uncontrolled trials. Further, there is no reliable evidence negating the utility of rTMS in the elderly with depression. We also identified several factors other than age that moderate the observed variations in the efficacy of rTMS in the elderly. These factors include but not limited to: (1) brain atrophy; (2) intensity and number of pulses (dose-response relationship); and (3) clinical profile of patients. On the basis of the current evidence, the practice of excluding elderly patients from TMS clinics and trials cannot be supported.
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14
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Rutherford G, Lithgow B, Moussavi Z. Short and Long-term Effects of rTMS Treatment on Alzheimer's Disease at Different Stages: A Pilot Study. J Exp Neurosci 2015; 9:43-51. [PMID: 26064066 PMCID: PMC4457230 DOI: 10.4137/jen.s24004] [Citation(s) in RCA: 75] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Revised: 04/06/2015] [Accepted: 04/10/2015] [Indexed: 12/03/2022] Open
Abstract
Repetitive transcranial magnetic stimulation (rTMS) uses a magnetic coil to induce an electric field in brain tissue. As a pilot study, we investigated the effect of rTMS treatment on 10 volunteers with Alzheimer’s disease (AD) in a two-stage study. The first stage consisted of a double-blind crossover study with real and sham treatments. Each treatment block consisted of 13 sessions over 4 weeks. During each session, 2000 TMS pulses at 90%–100% of resting motor threshold were applied to dorsolateral prefrontal cortex bilaterally, and the patients were kept cognitively active by object/action naming during the treatment. The second stage was an open-label study, in which the same treatments were performed in 2-week blocks (10 sessions) approximately every 3 months as follow-up treatments on six of the volunteers, who completed the first stage of the study. Primary outcome measures were the Montreal Cognitive Assessment (MOCA) and the Alzheimer’s Disease Assessment Scale-cognitive subscale. The secondary outcome measures were the Revised Memory and Behavior Checklist as well as our team’s custom-designed cognitive assessments. The results showed a noticeably stronger improvement on all assessments during the real treatment as compared to the sham treatment. The changes in MOCA scores as well as our designed cognitive assessment were found to be statistically significant, with particularly strong results in the six volunteers who were in the early stages of the disease. The long-term trends observed in the second stage of the study also showed generally less decline than would be expected for their condition. It appears that rTMS can be an effective tool for improving the cognitive abilities of patients with early to moderate stages of AD. However, the positive effects of rTMS may persist for only up to a few weeks. Specific skills being practiced during rTMS treatment may retain their improvement for longer periods.
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Affiliation(s)
- Grant Rutherford
- Biomedical Engineering Program, University of Manitoba, Winnipeg, Canada
| | - Brian Lithgow
- Biomedical Engineering Program, University of Manitoba, Winnipeg, Canada. ; Monash-Alfred Psychiatry Research Center, Melbourne, Australia
| | - Zahra Moussavi
- Biomedical Engineering Program and Psychiatry Department, University of Manitoba, Winnipeg, Canada
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15
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Devi G, Voss HU, Levine D, Abrassart D, Heier L, Halper J, Martin L, Lowe S. Open-label, short-term, repetitive transcranial magnetic stimulation in patients with Alzheimer's disease with functional imaging correlates and literature review. Am J Alzheimers Dis Other Demen 2014; 29:248-55. [PMID: 24421409 PMCID: PMC10852822 DOI: 10.1177/1533317513517047] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/03/2024]
Abstract
BACKGROUND Accumulating evidence suggests repetitive transcranial magnetic stimulation (rTMS) may be beneficial in ameliorating cognitive deficits in Alzheimer's disease (AD). METHODS AD patients received four high-frequency rTMS sessions over the bilateral dorsolateral prefrontal cortex (DLPFC) over two weeks. Structured cognitive assessments were administered at baseline, at 2 weeks after completion of rTMS, and at 4 weeks post treatment. At these same times, tolerant patients underwent functional magnetic resonance imaging (fMRI) while performing structured motor and cognitive tasks. We also reviewed literature regarding the effects of rTMS on cognitive function in AD. RESULTS A total of 12 patients were enrolled, eight of whom tolerated the fMRI. Improvement was seen in Boston Diagnostic Aphasia Examination tests of verbal and non-verbal agility 4 weeks post-treatment. The fMRI analysis showed trends for increased activation during cognitive performance tasks immediately after and at 4 weeks post-treatment. Our literature review revealed several double-blind, sham-controlled studies, all showing sustained improvement in cognition of AD patients with rTMS. CONCLUSIONS There was improvement in aspects of language after four rTMS treatments, sustained a month after treatment cessation. Our results are consistent with other studies and standardization of treatment protocols using functional imaging may be of benefit.
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Affiliation(s)
- Gayatri Devi
- New York Memory and Healthy Aging Services, New York, NY, USA
- Department of Neurology, New York University School of Medicine, New York, NY, USA
- Department of Psychiatry, New York University School of Medicine, New York, NY, USA
| | - Henning U. Voss
- Department of Radiology, Weill Cornell Medical College, New York, NY, USA
| | - Dani Levine
- New York Memory and Healthy Aging Services, New York, NY, USA
| | - Dana Abrassart
- New York Memory and Healthy Aging Services, New York, NY, USA
| | - Linda Heier
- Department of Radiology, Weill Cornell Medical College, New York, NY, USA
| | - James Halper
- New York Memory and Healthy Aging Services, New York, NY, USA
- Department of Psychiatry, New York University School of Medicine, New York, NY, USA
| | - Leilanie Martin
- New York Memory and Healthy Aging Services, New York, NY, USA
| | - Sandy Lowe
- New York Memory and Healthy Aging Services, New York, NY, USA
- Department of Psychiatry, New York University School of Medicine, New York, NY, USA
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