Genetic Etiology Influences the Low-Frequency Components of Globus Pallidus Internus Electrophysiology in Dystonia

Ahmet Kaymak; Luigi M. Romito; Fabiana Colucci; Nico Golfrè Andreasi; Roberta Telese; Sara Rinaldo; Vincenzo Levi; Giovanna Zorzi; Zvi Israel; David Arkadir; Hagai Bergman; Miryam Carecchio; Holger Prokisch; Michael Zech; Barbara Garavaglia; Alberto Mazzoni; Roberto Eleopra

doi:10.1111/ene.70098

Genetic Etiology Influences the Low-Frequency Components of Globus Pallidus Internus Electrophysiology in Dystonia

Ahmet Kaymak, Luigi M. Romito^*, Fabiana Colucci, Nico Golfrè Andreasi, Roberta Telese, Sara Rinaldo, Vincenzo Levi, Giovanna Zorzi, Zvi Israel, David Arkadir, Hagai Bergman, Miryam Carecchio, Holger Prokisch, Michael Zech, Barbara Garavaglia, Alberto Mazzoni^*, Roberto Eleopra

^*Corresponding author for this work

Edmond & Lily Safra Center for Brain Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Elevated low-frequency activity (4–12 Hz) within the globus pallidus internus (GPi) has been consistently associated with dystonia. However, the impacts of the genetic etiology of dystonia on low-frequency GPi activity remain unclear; yet it holds importance for adaptive deep brain stimulation (DBS) treatment. Methods: We compared the properties of GPi electrophysiology acquired from 70 microelectrode recordings (MER) trajectories of DYT-GNAL, DYT-KMT2B, DYT-SGCE, DYT-THAP1, DYT-TOR1A, DYT-VPS16, and idiopathic dystonia (iDYT) patients who underwent GPi-DBS surgery across standard frequency bands. Results: DYT-SGCE patients exhibited significantly lower alpha band activity (2.97%) compared to iDYT (4.44%, p = 0.006) and DYT-THAP1 (4.51%, p = 0.011). Additionally, theta band power was also significantly reduced in DYT-SGCE (4.42%) compared to iDYT and DYT-THAP1 (7.91% and 7.00%, p < 0.05). Instead, the genetic etiology of dystonia did not affect the spatial characteristics of GPi electrophysiology along MER trajectories. Conclusion: Considering the genetic etiology of dystonia in closed-loop DBS treatments and utilizing theta and alpha activity for GPi stimulation may optimize clinical outcomes. MER-based DBS lead placement can proceed independently of the underlying genetic cause.

Original language	English
Article number	e70098
Journal	European Journal of Neurology
Volume	32
Issue number	3
DOIs	https://doi.org/10.1111/ene.70098
State	Published - Mar 2025

Bibliographical note

Publisher Copyright:
© 2025 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

Keywords

alpha oscillations
deep brain stimulation
dystonia
electrophysiology
genetics

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10.1111/ene.70098

Cite this

Kaymak, A., Romito, L. M., Colucci, F., Andreasi, N. G., Telese, R., Rinaldo, S., Levi, V., Zorzi, G., Israel, Z., Arkadir, D., Bergman, H., Carecchio, M., Prokisch, H., Zech, M., Garavaglia, B., Mazzoni, A., & Eleopra, R. (2025). Genetic Etiology Influences the Low-Frequency Components of Globus Pallidus Internus Electrophysiology in Dystonia. European Journal of Neurology, 32(3), Article e70098. https://doi.org/10.1111/ene.70098

@article{63cd932c447648eca475f2a7f28820ad,

title = "Genetic Etiology Influences the Low-Frequency Components of Globus Pallidus Internus Electrophysiology in Dystonia",

abstract = "Background: Elevated low-frequency activity (4–12 Hz) within the globus pallidus internus (GPi) has been consistently associated with dystonia. However, the impacts of the genetic etiology of dystonia on low-frequency GPi activity remain unclear; yet it holds importance for adaptive deep brain stimulation (DBS) treatment. Methods: We compared the properties of GPi electrophysiology acquired from 70 microelectrode recordings (MER) trajectories of DYT-GNAL, DYT-KMT2B, DYT-SGCE, DYT-THAP1, DYT-TOR1A, DYT-VPS16, and idiopathic dystonia (iDYT) patients who underwent GPi-DBS surgery across standard frequency bands. Results: DYT-SGCE patients exhibited significantly lower alpha band activity (2.97%) compared to iDYT (4.44%, p = 0.006) and DYT-THAP1 (4.51%, p = 0.011). Additionally, theta band power was also significantly reduced in DYT-SGCE (4.42%) compared to iDYT and DYT-THAP1 (7.91% and 7.00%, p < 0.05). Instead, the genetic etiology of dystonia did not affect the spatial characteristics of GPi electrophysiology along MER trajectories. Conclusion: Considering the genetic etiology of dystonia in closed-loop DBS treatments and utilizing theta and alpha activity for GPi stimulation may optimize clinical outcomes. MER-based DBS lead placement can proceed independently of the underlying genetic cause.",

keywords = "alpha oscillations, deep brain stimulation, dystonia, electrophysiology, genetics",

author = "Ahmet Kaymak and Romito, {Luigi M.} and Fabiana Colucci and Andreasi, {Nico Golfr{\`e}} and Roberta Telese and Sara Rinaldo and Vincenzo Levi and Giovanna Zorzi and Zvi Israel and David Arkadir and Hagai Bergman and Miryam Carecchio and Holger Prokisch and Michael Zech and Barbara Garavaglia and Alberto Mazzoni and Roberto Eleopra",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.",

year = "2025",

month = mar,

doi = "10.1111/ene.70098",

language = "אנגלית",

volume = "32",

journal = "European Journal of Neurology",

issn = "1351-5101",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "3",

}

Kaymak, A, Romito, LM, Colucci, F, Andreasi, NG, Telese, R, Rinaldo, S, Levi, V, Zorzi, G, Israel, Z, Arkadir, D, Bergman, H, Carecchio, M, Prokisch, H, Zech, M, Garavaglia, B, Mazzoni, A & Eleopra, R 2025, 'Genetic Etiology Influences the Low-Frequency Components of Globus Pallidus Internus Electrophysiology in Dystonia', European Journal of Neurology, vol. 32, no. 3, e70098. https://doi.org/10.1111/ene.70098

TY - JOUR

T1 - Genetic Etiology Influences the Low-Frequency Components of Globus Pallidus Internus Electrophysiology in Dystonia

AU - Kaymak, Ahmet

AU - Romito, Luigi M.

AU - Colucci, Fabiana

AU - Andreasi, Nico Golfrè

AU - Telese, Roberta

AU - Rinaldo, Sara

AU - Levi, Vincenzo

AU - Zorzi, Giovanna

AU - Israel, Zvi

AU - Arkadir, David

AU - Bergman, Hagai

AU - Carecchio, Miryam

AU - Prokisch, Holger

AU - Zech, Michael

AU - Garavaglia, Barbara

AU - Mazzoni, Alberto

AU - Eleopra, Roberto

PY - 2025/3

Y1 - 2025/3

N2 - Background: Elevated low-frequency activity (4–12 Hz) within the globus pallidus internus (GPi) has been consistently associated with dystonia. However, the impacts of the genetic etiology of dystonia on low-frequency GPi activity remain unclear; yet it holds importance for adaptive deep brain stimulation (DBS) treatment. Methods: We compared the properties of GPi electrophysiology acquired from 70 microelectrode recordings (MER) trajectories of DYT-GNAL, DYT-KMT2B, DYT-SGCE, DYT-THAP1, DYT-TOR1A, DYT-VPS16, and idiopathic dystonia (iDYT) patients who underwent GPi-DBS surgery across standard frequency bands. Results: DYT-SGCE patients exhibited significantly lower alpha band activity (2.97%) compared to iDYT (4.44%, p = 0.006) and DYT-THAP1 (4.51%, p = 0.011). Additionally, theta band power was also significantly reduced in DYT-SGCE (4.42%) compared to iDYT and DYT-THAP1 (7.91% and 7.00%, p < 0.05). Instead, the genetic etiology of dystonia did not affect the spatial characteristics of GPi electrophysiology along MER trajectories. Conclusion: Considering the genetic etiology of dystonia in closed-loop DBS treatments and utilizing theta and alpha activity for GPi stimulation may optimize clinical outcomes. MER-based DBS lead placement can proceed independently of the underlying genetic cause.

AB - Background: Elevated low-frequency activity (4–12 Hz) within the globus pallidus internus (GPi) has been consistently associated with dystonia. However, the impacts of the genetic etiology of dystonia on low-frequency GPi activity remain unclear; yet it holds importance for adaptive deep brain stimulation (DBS) treatment. Methods: We compared the properties of GPi electrophysiology acquired from 70 microelectrode recordings (MER) trajectories of DYT-GNAL, DYT-KMT2B, DYT-SGCE, DYT-THAP1, DYT-TOR1A, DYT-VPS16, and idiopathic dystonia (iDYT) patients who underwent GPi-DBS surgery across standard frequency bands. Results: DYT-SGCE patients exhibited significantly lower alpha band activity (2.97%) compared to iDYT (4.44%, p = 0.006) and DYT-THAP1 (4.51%, p = 0.011). Additionally, theta band power was also significantly reduced in DYT-SGCE (4.42%) compared to iDYT and DYT-THAP1 (7.91% and 7.00%, p < 0.05). Instead, the genetic etiology of dystonia did not affect the spatial characteristics of GPi electrophysiology along MER trajectories. Conclusion: Considering the genetic etiology of dystonia in closed-loop DBS treatments and utilizing theta and alpha activity for GPi stimulation may optimize clinical outcomes. MER-based DBS lead placement can proceed independently of the underlying genetic cause.

KW - alpha oscillations

KW - deep brain stimulation

KW - dystonia

KW - electrophysiology

KW - genetics

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U2 - 10.1111/ene.70098

DO - 10.1111/ene.70098

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C2 - 40062447

AN - SCOPUS:105000000522

SN - 1351-5101

VL - 32

JO - European Journal of Neurology

JF - European Journal of Neurology

IS - 3

M1 - e70098

ER -

Genetic Etiology Influences the Low-Frequency Components of Globus Pallidus Internus Electrophysiology in Dystonia

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Keywords

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