[en] This study addresses a critical dilemma in brain tumor (BT) neurosurgery, where surgeons must balance the goal of removing as much of the tumor as possible with the need to preserve healthy brain tissue. On the one hand, gross or supratotal resection of the tumor helps to reduce the risk of recurrence, but it may increase the likelihood of damaging surrounding healthy brain tissue, which could lead to functional impairments. On the other hand, a less radical resection may protect brain function, but it leaves behind cancerous cells that could cause the tumor to reoccur. To address this challenge, novel approaches like Neuromodulation-Induced Cortical Prehabilitation (NICP) have been explored as a way to optimize neurosurgical outcomes by expanding the functional margins that allow for safe, radical tumor removal. NICP combines neuromodulation and task-specific training to influence brain plasticity. Neuromodulation aims to inhibit activity in peritumoral eloquent areas, while task-specific training encourages alternative brain regions to take over these functions. This strategy helps to shift the brain's functional load away from eloquent areas at risk during surgery, thus reducing the likelihood of functional deficits. Although previous studies of NICP are limited to just a few cases, the findings suggest that invasive approaches are more effective than non-invasive ones in inducing neuroplastic changes. However, the invasive methods come with higher risks, including infection and seizures. In contrast, non-invasive techniques such as Transcranial Magnetic Stimulation (TMS) are safer but have shown limited effectiveness, possibly due to insufficient task-specific training. In response to these findings, the Institut Guttmann in Barcelona developed a novel protocol for non-invasive NICP, combining it with intensive task training in a pilot study involving 10 patients as part of the 'PREHABILITA' thesis. This was followed by a larger ongoing trial with 20 more patients. The intervention included 10 to 20 sessions of non-invasive brain stimulation (TMS or transcranial Direct Current Stimulation (tDCS)), focused on upper limb motor function, language, or cognitive abilities depending on the patient's needs. Before, during, and after surgery, comprehensive neuroimaging and clinical assessments were conducted to monitor changes in brain function, quality of life, and neuroplasticity. The primary goal of the study was to assess the feasibility of the protocol in terms of patient adherence, safety, and satisfaction. Additionally, the study sought to explore the effectiveness of the intervention and identify key factors that contribute to successful outcomes. The results were promising: the intervention was feasible, with high adherence and retention rates, and no adverse events attributable to the treatment. All patients completed the program without experiencing functional decline, and they expressed satisfaction with the therapy. Neuroimaging data revealed an overall trend for increased distance between eloquent brain areas and both the neuromodulation target and the tumor, suggesting a shift in brain activity away from areas at risk during surgery. However, outcomes varied on a case-by-case basis, with some patients showing substantial neuroplastic changes and others experiencing minimal or even undesirable changes. Additional analyses indicated that the most consistent neuroplastic changes occurred when the neuromodulation target was focused on areas of peak activity as identified by functional MRI (fMRI), particularly when targeting the eloquent area itself rather than more distant brain regions. This research represents the largest case series of NICP to date and demonstrates that non-invasive NICP, combined with intensive task training, is both feasible and capable of inducing meaningful neuroplastic changes before neurosurgery. While these early results are encouraging, larger cohort studies are needed to validate the findings and further refine the methodology developed in this study.

[es] Este estudio aborda el dilema en la neurocirugía de tumores cerebrales: extirpar la mayor cantidad de tumor para reducir el riesgo de recurrencia, con el peligro de dañar tejido cerebral sano, o preservar la función cerebral dejando células tumorales que podrían causar una rápida recurrencia. La Prehabilitación Cortical Inducida por Neuromodulación (NICP) busca resolver este conflicto al optimizar la neurocirugía mediante la expansión de los márgenes funcionales para la extirpación segura del tumor. La NICP combina neuromodulación y entrenamiento específico en tareas para inhibir áreas elocuentes peritumorales y activar otras zonas cerebrales, fomentando la plasticidad neuronal. Aunque hay pocos estudios previos, los enfoques invasivos de NICP han demostrado ser efectivos pero riesgosos, mientras que los no invasivos (como la Estimulación Magnética Transcraneal, TMS) son más seguros pero menos efectivos. En el Institut Guttmann (Barcelona), se desarrolló un protocolo innovador de NICP no invasiva con entrenamiento intensivo. Este protocolo fue validado en un estudio piloto de 10 pacientes como parte de la tesis 'PREHABILITA', seguido de un ensayo en curso con 20 pacientes adicionales. La intervención consistió en entre 10 y 20 sesiones de estimulación cerebral no invasiva (TMS o tDCS) con entrenamiento en función motora, del lenguaje o cognitiva, según el riesgo individual. Se realizaron evaluaciones clínicas y neurofisiológicas antes, durante y después de la cirugía. Los resultados preliminares mostraron que el protocolo es viable, con altas tasas de adherencia y sin eventos adversos relacionados con la intervención. No hubo deterioro funcional en los pacientes, quienes mostraron satisfacción con el tratamiento. Los datos de neuroimagen revelaron un aumento de la distancia entre las áreas elocuentes y el tumor, sugiriendo cambios neuroplásticos en algunos pacientes. Sin embargo, estos resultados variaron, con algunos casos mostrando cambios menores o no deseados. Se observó que los cambios neuroplásticos más consistentes ocurrieron cuando la neuromodulación se dirigía a áreas de máxima actividad identificadas por fMRI. Esta investigación representa la mayor serie de casos sobre NICP hasta la fecha, demostrando que la NICP no invasiva combinada con entrenamiento intensivo en tareas es factible y puede inducir cambios neuroplásticos clínicamente relevantes antes de la cirugía. Estos resultados son prometedores, pero es necesario validar los hallazgos en estudios con cohortes más grandes.