Motor network reorganization associated with rTMS-induced writing improvement in writer's cramp dystonia

Background: Writer's cramp (WC) dystonia is an involuntary movement disorder with distributed abnormalities in the brain's motor network. Prior studies established the potential for repetitive transcranial magnetic stimulation (rTMS) to either premotor cortex (PMC) or primary somatosensory...

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Main Authors: Noreen Bukhari-Parlakturk, Patrick J. Mulcahey, Michael W. Lutz, Rabia Ghazi, Ziping Huang, Moritz Dannhauer, Pichet Termsarasab, Burton Scott, Zeynep B. Simsek, Skylar Groves, Mikaela Lipp, Michael Fei, Tiffany K. Tran, Eleanor Wood, Lysianne Beynel, Chris Petty, James T. Voyvodic, Lawrence G. Appelbaum, Hussein R. Al-Khalidi, Simon W. Davis, Andrew M. Michael, Angel V. Peterchev, Nicole Calakos
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Brain Stimulation
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Online Access:http://www.sciencedirect.com/science/article/pii/S1935861X25000361
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author Noreen Bukhari-Parlakturk
Patrick J. Mulcahey
Michael W. Lutz
Rabia Ghazi
Ziping Huang
Moritz Dannhauer
Pichet Termsarasab
Burton Scott
Zeynep B. Simsek
Skylar Groves
Mikaela Lipp
Michael Fei
Tiffany K. Tran
Eleanor Wood
Lysianne Beynel
Chris Petty
James T. Voyvodic
Lawrence G. Appelbaum
Hussein R. Al-Khalidi
Simon W. Davis
Andrew M. Michael
Angel V. Peterchev
Nicole Calakos
author_facet Noreen Bukhari-Parlakturk
Patrick J. Mulcahey
Michael W. Lutz
Rabia Ghazi
Ziping Huang
Moritz Dannhauer
Pichet Termsarasab
Burton Scott
Zeynep B. Simsek
Skylar Groves
Mikaela Lipp
Michael Fei
Tiffany K. Tran
Eleanor Wood
Lysianne Beynel
Chris Petty
James T. Voyvodic
Lawrence G. Appelbaum
Hussein R. Al-Khalidi
Simon W. Davis
Andrew M. Michael
Angel V. Peterchev
Nicole Calakos
author_sort Noreen Bukhari-Parlakturk
collection DOAJ
description Background: Writer's cramp (WC) dystonia is an involuntary movement disorder with distributed abnormalities in the brain's motor network. Prior studies established the potential for repetitive transcranial magnetic stimulation (rTMS) to either premotor cortex (PMC) or primary somatosensory cortex (PSC) to modify symptoms. However, clinical effects have been modest with limited understanding of the neural mechanisms hindering therapeutic advancement of this promising approach. Objective: This study aimed to understand the motor network effects of rTMS in WC that correspond with behavioral efficacy. We hypothesized that behavioral efficacy is associated with modulation of cortical and subcortical regions of the motor network. Methods: In a double-blind, cross-over design, twelve WC participants underwent rTMS in one of three conditions (Sham-TMS, 10 Hz PSC-rTMS, 10 Hz PMC-rTMS) while engaged in a writing task to activate dystonic movements and measure writing fluency. Brain connectivity was evaluated using task-based fMRI after each TMS session. Results: 10 Hz rTMS to PSC, but not PMC, significantly improved writing dysfluency. PSC-TMS also significantly weakened cortico-basal ganglia, cortico-cerebellum, and intra-cerebellum functional connectivity (FC), and strengthened striatal FC relative to Sham. Change in PSC and SPC BOLD activity were associated with reduced dysfluent writing behavior. Conclusions: 10 Hz rTMS to PSC improved writing dysfluency by redistributing motor network connectivity and strengthening somatosensory-parietal connectivity. A key signature for effective stimulation at PSC and improvement in writing dysfluency may be strengthening of intra-cortical connectivity between primary somatosensory and superior parietal cortices. These findings offer mechanistic hypotheses to advance the therapeutic application of TMS for dystonia.
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spelling doaj-art-83292cbf40cf4e3487e254b667eec7792025-08-20T02:12:08ZengElsevierBrain Stimulation1935-861X2025-03-0118219821010.1016/j.brs.2025.02.005Motor network reorganization associated with rTMS-induced writing improvement in writer's cramp dystoniaNoreen Bukhari-Parlakturk0Patrick J. Mulcahey1Michael W. Lutz2Rabia Ghazi3Ziping Huang4Moritz Dannhauer5Pichet Termsarasab6Burton Scott7Zeynep B. Simsek8Skylar Groves9Mikaela Lipp10Michael Fei11Tiffany K. Tran12Eleanor Wood13Lysianne Beynel14Chris Petty15James T. Voyvodic16Lawrence G. Appelbaum17Hussein R. Al-Khalidi18Simon W. Davis19Andrew M. Michael20Angel V. Peterchev21Nicole Calakos22Department of Neurology, Duke University School of Medicine, USA; Duke Institute for Brain Sciences, Duke University, USA; Corresponding author. DUMC Box 2900, Bryan Research Building, 311 Research Drive, Durham, NC, 27710, USA.Department of Neurology, Duke University School of Medicine, USADepartment of Neurology, Duke University School of Medicine, USADepartment of Neurology, Duke University School of Medicine, USADepartment of Neurology, Duke University School of Medicine, USADepartment of Computer Science, Center for Brain Stimulation, East Carolina University, Greenville, NC, USADepartment of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandDepartment of Neurology, Duke University School of Medicine, USADepartment of Neurology, Duke University School of Medicine, USADepartment of Neurology, Duke University School of Medicine, USADepartment of Neurology, Duke University School of Medicine, USADepartment of Neurology, Duke University School of Medicine, USADepartment of Neurology, Duke University School of Medicine, USADrexel University College of Medicine, Philadelphia, PA, USANon Invasive Neuromodulation Unit, Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institute of Health, Bethesda, MD, USABrain Imaging & Analysis Center, Duke University School of Medicine, USADuke Institute for Brain Sciences, Duke University, USA; Brain Imaging & Analysis Center, Duke University School of Medicine, USADepartment of Psychiatry, University of California, San Diego, CA, USADepartment of Biostatistics and Bioinformatics, Duke University School of Medicine, USADepartment of Neurology, Duke University School of Medicine, USA; Duke Institute for Brain Sciences, Duke University, USADuke Institute for Brain Sciences, Duke University, USADuke Institute for Brain Sciences, Duke University, USA; Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, USA; Department of Electrical and Computer Engineering, Duke University, USA; Department of Neurosurgery, Duke University School of Medicine, USA; Department of Biomedical Engineering, Duke University, USADepartment of Neurology, Duke University School of Medicine, USA; Duke Institute for Brain Sciences, Duke University, USA; Department of Neurobiology, Duke University School of Medicine, Durham, NC, USABackground: Writer's cramp (WC) dystonia is an involuntary movement disorder with distributed abnormalities in the brain's motor network. Prior studies established the potential for repetitive transcranial magnetic stimulation (rTMS) to either premotor cortex (PMC) or primary somatosensory cortex (PSC) to modify symptoms. However, clinical effects have been modest with limited understanding of the neural mechanisms hindering therapeutic advancement of this promising approach. Objective: This study aimed to understand the motor network effects of rTMS in WC that correspond with behavioral efficacy. We hypothesized that behavioral efficacy is associated with modulation of cortical and subcortical regions of the motor network. Methods: In a double-blind, cross-over design, twelve WC participants underwent rTMS in one of three conditions (Sham-TMS, 10 Hz PSC-rTMS, 10 Hz PMC-rTMS) while engaged in a writing task to activate dystonic movements and measure writing fluency. Brain connectivity was evaluated using task-based fMRI after each TMS session. Results: 10 Hz rTMS to PSC, but not PMC, significantly improved writing dysfluency. PSC-TMS also significantly weakened cortico-basal ganglia, cortico-cerebellum, and intra-cerebellum functional connectivity (FC), and strengthened striatal FC relative to Sham. Change in PSC and SPC BOLD activity were associated with reduced dysfluent writing behavior. Conclusions: 10 Hz rTMS to PSC improved writing dysfluency by redistributing motor network connectivity and strengthening somatosensory-parietal connectivity. A key signature for effective stimulation at PSC and improvement in writing dysfluency may be strengthening of intra-cortical connectivity between primary somatosensory and superior parietal cortices. These findings offer mechanistic hypotheses to advance the therapeutic application of TMS for dystonia.http://www.sciencedirect.com/science/article/pii/S1935861X25000361Writer's crampMotor networkTranscranial magnetic stimulationDystonia
spellingShingle Noreen Bukhari-Parlakturk
Patrick J. Mulcahey
Michael W. Lutz
Rabia Ghazi
Ziping Huang
Moritz Dannhauer
Pichet Termsarasab
Burton Scott
Zeynep B. Simsek
Skylar Groves
Mikaela Lipp
Michael Fei
Tiffany K. Tran
Eleanor Wood
Lysianne Beynel
Chris Petty
James T. Voyvodic
Lawrence G. Appelbaum
Hussein R. Al-Khalidi
Simon W. Davis
Andrew M. Michael
Angel V. Peterchev
Nicole Calakos
Motor network reorganization associated with rTMS-induced writing improvement in writer's cramp dystonia
Brain Stimulation
Writer's cramp
Motor network
Transcranial magnetic stimulation
Dystonia
title Motor network reorganization associated with rTMS-induced writing improvement in writer's cramp dystonia
title_full Motor network reorganization associated with rTMS-induced writing improvement in writer's cramp dystonia
title_fullStr Motor network reorganization associated with rTMS-induced writing improvement in writer's cramp dystonia
title_full_unstemmed Motor network reorganization associated with rTMS-induced writing improvement in writer's cramp dystonia
title_short Motor network reorganization associated with rTMS-induced writing improvement in writer's cramp dystonia
title_sort motor network reorganization associated with rtms induced writing improvement in writer s cramp dystonia
topic Writer's cramp
Motor network
Transcranial magnetic stimulation
Dystonia
url http://www.sciencedirect.com/science/article/pii/S1935861X25000361
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