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Biomedicines
Volume 13
Issue 12
10.3390/biomedicines13123068
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Systematic Review

Effects of Transcranial Neuromodulation on Rehabilitation Outcomes After Anterior Cruciate Ligament Injury: A Systematic Review of Randomized Controlled Trials

by
Juan Vicente-Mampel
1,
Mariola Belda-Antolí
1,
Eloy Jaenada-Carrilero
1,
Andrés Pascual-Leone
2,
Luís Baraja-Vegas
1,
Nicolás Pascual-Leone
3,
Javier Ferrer-Torregrosa
4,*,
Francisco J. Falaguera-Vera
1,
Álvaro Pascual-Leone
5,6,† and
José María Tormos-Muñoz
7,†
1
School of Medicine and Health Science, Department of Physiotherapy, Catholic University of Valencia, 46001 Valencia, Spain
2
Department of Neurosurgery, Columbia University, New York, NY 10027, USA
3
Hospital for Special Surgery, New York, NY 10021, USA
4
School of Medicine and Health Science, Department of Podiatry, Catholic University of Valencia, 46001 Valencia, Spain
5
Marcus Institute for Aging Research and Wolk Center for Memory Health, Hebrew SeniorLife, Boston, MA 02131, USA
6
Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
7
School of Medicine and Health Science, Department of Medicine, Catholic University of Valencia, 46001 Valencia, Spain
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biomedicines 2025, 13(12), 3068; https://doi.org/10.3390/biomedicines13123068
Submission received: 18 September 2025 / Revised: 27 November 2025 / Accepted: 10 December 2025 / Published: 12 December 2025
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
Versions Notes

Abstract

Background/Objectives: Anterior cruciate ligament (ACL) injuries frequently lead to long-term quadriceps impairments despite surgical repair. There is growing evidence that these deficits are caused in part by alterations in the central nervous system. Thus, transcranial neuromodulation (TNM) could be valuable in ACL rehabilitation. To systematically review randomized controlled trials (RCTs) assessing the effects of TNM on neurophysiological, functional, and safety outcomes in patients with ACL injury or reconstruction. Methods: We conducted searches on PubMed, Scopus, Web of Science, and Cochrane. We considered all original studies evaluating TNM, including transcranial current stimulation (tCS) and transcranial magnetic stimulation (TMS), in patients with ACL reconstruction or injury. Measures of corticospinal excitability, safety, balance, and muscle strength were assessed. We employed the Cochrane RoB 2 method to assess the risk of bias. Results: Seven studies comprising 129 participants (64 TNM, 65 controls) were included. Most studies applied transcranial direct current stimulation (tDCS) over the primary motor cortex contralateral to the ACL injury in conjunction with physical rehabilitation. Single-session protocols demonstrated minimal effects, whereas repeated sessions resulted in improvements in corticospinal excitability, quadriceps strength, and balance. No serious adverse events were reported; minor effects included transient headache or scalp tingling. The risk of bias was assessed as low to moderate across the studies. Conclusions: TNM appears to be safe and may enhance functional recovery in individuals with ACL injuries when administered in multiple sessions alongside standard rehabilitation. Further high-quality trials are necessary to determine optimal protocols and long-term outcomes.
Keywords: ACL injury; central nervous system; cortical excitability; muscle strength; neuroplasticity; neuromodulation; tDCS ACL injury; central nervous system; cortical excitability; muscle strength; neuroplasticity; neuromodulation; tDCS

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MDPI and ACS Style

Vicente-Mampel, J.; Belda-Antolí, M.; Jaenada-Carrilero, E.; Pascual-Leone, A.; Baraja-Vegas, L.; Pascual-Leone, N.; Ferrer-Torregrosa, J.; Falaguera-Vera, F.J.; Pascual-Leone, Á.; Tormos-Muñoz, J.M. Effects of Transcranial Neuromodulation on Rehabilitation Outcomes After Anterior Cruciate Ligament Injury: A Systematic Review of Randomized Controlled Trials. Biomedicines 2025, 13, 3068. https://doi.org/10.3390/biomedicines13123068

AMA Style

Vicente-Mampel J, Belda-Antolí M, Jaenada-Carrilero E, Pascual-Leone A, Baraja-Vegas L, Pascual-Leone N, Ferrer-Torregrosa J, Falaguera-Vera FJ, Pascual-Leone Á, Tormos-Muñoz JM. Effects of Transcranial Neuromodulation on Rehabilitation Outcomes After Anterior Cruciate Ligament Injury: A Systematic Review of Randomized Controlled Trials. Biomedicines. 2025; 13(12):3068. https://doi.org/10.3390/biomedicines13123068

Chicago/Turabian Style

Vicente-Mampel, Juan, Mariola Belda-Antolí, Eloy Jaenada-Carrilero, Andrés Pascual-Leone, Luís Baraja-Vegas, Nicolás Pascual-Leone, Javier Ferrer-Torregrosa, Francisco J. Falaguera-Vera, Álvaro Pascual-Leone, and José María Tormos-Muñoz. 2025. "Effects of Transcranial Neuromodulation on Rehabilitation Outcomes After Anterior Cruciate Ligament Injury: A Systematic Review of Randomized Controlled Trials" Biomedicines 13, no. 12: 3068. https://doi.org/10.3390/biomedicines13123068

APA Style

Vicente-Mampel, J., Belda-Antolí, M., Jaenada-Carrilero, E., Pascual-Leone, A., Baraja-Vegas, L., Pascual-Leone, N., Ferrer-Torregrosa, J., Falaguera-Vera, F. J., Pascual-Leone, Á., & Tormos-Muñoz, J. M. (2025). Effects of Transcranial Neuromodulation on Rehabilitation Outcomes After Anterior Cruciate Ligament Injury: A Systematic Review of Randomized Controlled Trials. Biomedicines, 13(12), 3068. https://doi.org/10.3390/biomedicines13123068

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