Currently submitted to: JMIR Research Protocols
Date Submitted: Jun 15, 2026
Open Peer Review Period: Jun 15, 2026 - Aug 10, 2026
(currently open for review)
Warning: This is an author submission that is not peer-reviewed or edited. Preprints - unless they show as "accepted" - should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information.
Neuromodulation-Induced Cortical Prehabilitation in High-Grade Glioma Close to the Motor Pathway: A Protocol for a Pilot Randomized Controlled Trial Using Navigated Transcranial Magnetic Stimulation
ABSTRACT
Background:
Neuromodulation-Induced Cortical Prehabilitation (NICP) is a novel concept aimed at promoting neuroplasticity prior to surgery in patients with gliomas near eloquent regions, potentially increasing the extent of resection and improving functional outcomes. Current evidence is limited to small case series with methodological heterogeneity.
Objective:
To evaluate, using navigated transcranial magnetic stimulation (nTMS), the neuroplastic changes induced by preoperative physical therapy, either alone or in combination with repetitive transcranial magnetic stimulation (rTMS), in patients with high-grade gliomas (HGGs) located near the motor pathways
Methods:
The presented work is designed as a multi-center, prospective, randomized pilot trial. Patients will be allocated into three groups: (A) control, (B) physical therapy, and (C) physical therapy + repetitive transcranial magnetic stimulation (rTMS). Motor cortex mapping and cortical excitability indices will be assessed before (baseline; T0) and after (preoperatively; T1) the prehabilitation protocol using chiefly nTMS; additional indices will be assessed using standardized single-pulse and paired-pulse TMS paradigms. Expected primary outcomes will be changes in motor cortical representations and in cortical excitability indices; secondary outcomes will include intraoperative neurophysiological findings, surgical extent of resection, postoperative neurological function and post-operative deficit recovery time.
Results:
Recruitment is expected to begin in April 2026. Data analysis will compare levels of subject’s cortical excitability and regression modeling of confounders.
Conclusions:
This trial aims to provide the first systematic evaluation of physical therapy alone and combined with rTMS as non-invasive NICP technique in HGG patients, potentially introducing new strategies to enhance surgical safety and functional recovery Clinical Trial: registered in TrailGov.com as NCT07471100 ID
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