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

doi:10.1016/j.brs.2025.02.005

. 2025 Mar-Apr;18(2):198-210.

doi: 10.1016/j.brs.2025.02.005. Epub 2025 Feb 7.

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

Noreen Bukhari-Parlakturk¹, Patrick J Mulcahey², Michael W Lutz², Rabia Ghazi², Ziping Huang², Moritz Dannhauer³, Pichet Termsarasab⁴, Burton Scott², Zeynep B Simsek², Skylar Groves², Mikaela Lipp², Michael Fei², Tiffany K Tran², Eleanor Wood⁵, Lysianne Beynel⁶, Chris Petty⁷, James T Voyvodic⁸, Lawrence G Appelbaum⁹, Hussein R Al-Khalidi¹⁰, Simon W Davis¹¹, Andrew M Michael¹², Angel V Peterchev¹³, Nicole Calakos¹⁴

Affiliations

¹ Department of Neurology, Duke University School of Medicine, USA; Duke Institute for Brain Sciences, Duke University, USA. Electronic address: noreen.bukhari@duke.edu.
² Department of Neurology, Duke University School of Medicine, USA.
³ Department of Computer Science, Center for Brain Stimulation, East Carolina University, Greenville, NC, USA.
⁴ Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
⁵ Drexel University College of Medicine, Philadelphia, PA, USA.
⁶ Non Invasive Neuromodulation Unit, Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institute of Health, Bethesda, MD, USA.
⁷ Brain Imaging & Analysis Center, Duke University School of Medicine, USA.
⁸ Duke Institute for Brain Sciences, Duke University, USA; Brain Imaging & Analysis Center, Duke University School of Medicine, USA.
⁹ Department of Psychiatry, University of California, San Diego, CA, USA.
¹⁰ Department of Biostatistics and Bioinformatics, Duke University School of Medicine, USA.
¹¹ Department of Neurology, Duke University School of Medicine, USA; Duke Institute for Brain Sciences, Duke University, USA.
¹² Duke Institute for Brain Sciences, Duke University, USA.
¹³ Duke 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, USA.
¹⁴ Department 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, USA.

PMID: 39924101
PMCID: PMC11994290 (available on 2026-03-01)
DOI: 10.1016/j.brs.2025.02.005

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

Noreen Bukhari-Parlakturk et al. Brain Stimul. 2025 Mar-Apr.

. 2025 Mar-Apr;18(2):198-210.

doi: 10.1016/j.brs.2025.02.005. Epub 2025 Feb 7.

Authors

Affiliations

¹ Department of Neurology, Duke University School of Medicine, USA; Duke Institute for Brain Sciences, Duke University, USA. Electronic address: noreen.bukhari@duke.edu.
² Department of Neurology, Duke University School of Medicine, USA.
³ Department of Computer Science, Center for Brain Stimulation, East Carolina University, Greenville, NC, USA.
⁴ Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
⁵ Drexel University College of Medicine, Philadelphia, PA, USA.
⁶ Non Invasive Neuromodulation Unit, Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institute of Health, Bethesda, MD, USA.
⁷ Brain Imaging & Analysis Center, Duke University School of Medicine, USA.
⁸ Duke Institute for Brain Sciences, Duke University, USA; Brain Imaging & Analysis Center, Duke University School of Medicine, USA.
⁹ Department of Psychiatry, University of California, San Diego, CA, USA.
¹⁰ Department of Biostatistics and Bioinformatics, Duke University School of Medicine, USA.
¹¹ Department of Neurology, Duke University School of Medicine, USA; Duke Institute for Brain Sciences, Duke University, USA.
¹² Duke Institute for Brain Sciences, Duke University, USA.
¹³ Duke 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, USA.
¹⁴ Department 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, USA.

PMID: 39924101
PMCID: PMC11994290 (available on 2026-03-01)
DOI: 10.1016/j.brs.2025.02.005

Abstract

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.

Keywords: Dystonia; Motor network; Transcranial magnetic stimulation; Writer's cramp.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: NOREEN BUKHARI-Parlakturk reports financial support was provided by Dystonia Medical Research Foundation. NOREEN BUKHARI-Parlakturk reports financial support was provided by Doris Duke Charitable Foundation. NOREEN BUKHARI-Parlakturk reports financial support was provided by American Academy of Neurology. NOREEN BUKHARI-Parlakturk reports financial support was provided by NIH NCATS (1KL2TR002554). NOREEN BUKHARI-Parlakturk reports financial support was provided by Dystonia Coalition. Angel Peterchev reports financial support was provided by National Institutes of Health (R01MH128422, R01NS117405). NOREEN BUKHARI-Parlakturk reports a relationship with Dystonia Medical Research Foundation that includes: board membership, funding grants, and travel reimbursement. Angel Peterchev reports a relationship with Rogue Research that includes: consulting or advisory. Angel Peterchev reports a relationship with Ampa that includes: board membership, consulting or advisory, and equity or stocks. Angel Peterchev reports a relationship with Magnetic Tides that includes: consulting or advisory and equity or stocks. Angel Peterchev reports a relationship with Soterix Medical Inc that includes: consulting or advisory. Angel Peterchev reports a relationship with MagVenture Inc that includes: equity or stocks and non-financial support. Angel Peterchev reports a relationship with Motif that includes: funding grants. Simon W. Davis reports a relationship with Neuronetics that includes: consulting or advisory. Angel V. Peterchev serves on the editorial board of the Brain Stimulation journal. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Update of

Motor network reorganization associated with rTMS-induced writing improvement in writer's cramp dystonia.
Bukhari-Parlakturk N, Mulcahey PJ, Lutz MW, Ghazi R, Huang Z, Dannhauer M, Termsarasab P, Scott B, Simsek ZB, Groves S, Lipp M, Fei M, Tran TK, Wood E, Beynel L, Petty C, Voyvodic JT, Appelbaum LG, Al-Khalidi HR, Davis SW, Michael AM, Peterchev AV, Calakos N. Bukhari-Parlakturk N, et al. medRxiv [Preprint]. 2025 Jan 18:2024.09.30.24314652. doi: 10.1101/2024.09.30.24314652. medRxiv. 2025. Update in: Brain Stimul. 2025 Mar-Apr;18(2):198-210. doi: 10.1016/j.brs.2025.02.005. PMID: 39867369 Free PMC article. Updated. Preprint.

Cited by

Increased sensorimotor and superior parietal activation correlate with reduced writing dysfluency in writer's cramp dystonia.
Bukhari-Parlakturk N, Mulcahey PJ, Fei M, Lutz MW, Voyvodic JT, Davis SW, Michael AM. Bukhari-Parlakturk N, et al. medRxiv [Preprint]. 2025 Mar 21:2025.03.20.25324331. doi: 10.1101/2025.03.20.25324331. medRxiv. 2025. PMID: 40166535 Free PMC article. Preprint.

References

1. Ortiz R, Scheperjans F, Mertsalmi T, Pekkonen E. The prevalence of adult-onset isolated dystonia in Finland 2007–2016. PLoS One. 2018;13(11):e0207729. - PMC - PubMed
1. Albanese A, Bhatia K, Bressman SB, Delong MR, Fahn S, Fung VS, et al. Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013;28(7):863–73. - PMC - PubMed
1. Morrison-Ham J, Clark GM, Ellis EG, Cerins A, Joutsa J, Enticott PG, et al. Effects of non-invasive brain stimulation in dystonia: a systematic review and meta-analysis. Ther Adv Neurol Disord. 2022;15:17562864221138144. - PMC - PubMed
1. Strafella AP, Ko JH, Grant J, Fraraccio M, Monchi O. Corticostriatal functional interactions in Parkinson’s disease: a rTMS/[11C]raclopride PET study. Eur J Neurosci. 2005;22(11):2946–52. - PMC - PubMed
1. Sack AT, Paneva J, Kuthe T, Dijkstra E, Zwienenberg L, Arns M, et al. Target Engagement and Brain State Dependence of Transcranial Magnetic Stimulation: Implications for Clinical Practice. Biol Psychiatry. 2024;95(6):536–44. - PubMed

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[1] Ortiz R, Scheperjans F, Mertsalmi T, Pekkonen E. The prevalence of adult-onset isolated dystonia in Finland 2007–2016. PLoS One. 2018;13(11):e0207729. - PMC - PubMed

[2] Ortiz R, Scheperjans F, Mertsalmi T, Pekkonen E. The prevalence of adult-onset isolated dystonia in Finland 2007–2016. PLoS One. 2018;13(11):e0207729. - PMC - PubMed

[3] Albanese A, Bhatia K, Bressman SB, Delong MR, Fahn S, Fung VS, et al. Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013;28(7):863–73. - PMC - PubMed

[4] Albanese A, Bhatia K, Bressman SB, Delong MR, Fahn S, Fung VS, et al. Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013;28(7):863–73. - PMC - PubMed

[5] Morrison-Ham J, Clark GM, Ellis EG, Cerins A, Joutsa J, Enticott PG, et al. Effects of non-invasive brain stimulation in dystonia: a systematic review and meta-analysis. Ther Adv Neurol Disord. 2022;15:17562864221138144. - PMC - PubMed

[6] Morrison-Ham J, Clark GM, Ellis EG, Cerins A, Joutsa J, Enticott PG, et al. Effects of non-invasive brain stimulation in dystonia: a systematic review and meta-analysis. Ther Adv Neurol Disord. 2022;15:17562864221138144. - PMC - PubMed

[7] Strafella AP, Ko JH, Grant J, Fraraccio M, Monchi O. Corticostriatal functional interactions in Parkinson’s disease: a rTMS/[11C]raclopride PET study. Eur J Neurosci. 2005;22(11):2946–52. - PMC - PubMed

[8] Strafella AP, Ko JH, Grant J, Fraraccio M, Monchi O. Corticostriatal functional interactions in Parkinson’s disease: a rTMS/[11C]raclopride PET study. Eur J Neurosci. 2005;22(11):2946–52. - PMC - PubMed

[9] Sack AT, Paneva J, Kuthe T, Dijkstra E, Zwienenberg L, Arns M, et al. Target Engagement and Brain State Dependence of Transcranial Magnetic Stimulation: Implications for Clinical Practice. Biol Psychiatry. 2024;95(6):536–44. - PubMed

[10] Sack AT, Paneva J, Kuthe T, Dijkstra E, Zwienenberg L, Arns M, et al. Target Engagement and Brain State Dependence of Transcranial Magnetic Stimulation: Implications for Clinical Practice. Biol Psychiatry. 2024;95(6):536–44. - PubMed

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

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

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