Magnetic Pulses Over the Brain May Predict Glioblastoma Survival Before Surgery

A team of neurosurgeons and clinical neurophysiologists at King’s College Hospital in London has reported that a non-invasive brain stimulation technique, performed before surgery, can independently predict how long patients with glioblastoma are likely to live. The study, published in the Journal of Neuro-Oncology, used navigated transcranial magnetic stimulation, or nTMS, to measure the excitability of the motor cortex in seventy-seven patients undergoing resection of WHO grade 4, IDH-wildtype glioblastomas located in or near the brain’s motor regions. What the researchers found is striking: two simple scores derived from these stimulation measurements carried prognostic information that persisted even after accounting for the established clinical and molecular factors that oncologists normally rely upon, including age, sex, neurological deficit, MGMT promoter methylation and the extent of surgical resection.

The technique behind the finding is conceptually elegant. Transcranial magnetic stimulation uses a focused magnetic coil held over the scalp to induce small electrical currents in the underlying cortex, briefly provoking neurons and recording the muscular response, typically a twitch in a hand or arm muscle detected by electromyography. By systematically stimulating a grid of positions over the primary motor cortex and measuring the minimum stimulation intensity needed to evoke a response at each spot, clinicians can build a functional map of the motor system without opening the skull. When this procedure is combined with neuronavigation, which tracks the coil’s position against the patient’s magnetic resonance imaging, the resulting map can be used both to plan surgery and, as this study demonstrates, to extract quantitative measures of how excitable the motor cortex has become in the presence of a tumor.

The London group distilled their nTMS recordings into two composite metrics. The first, the IntraM1 Excitability Score, or IMES, summarizes excitability measures within the primary motor cortex itself, the region conventionally labeled M1. The second, the Cortical Excitability Score, or CES, aggregates a broader profile of excitability across the mapped cortical area. Higher IMES values and lower CES values both point toward a motor cortex that retains more of its normal responsiveness to stimulation. The team reasoned that if a growing glioblastoma progressively disrupts the physiological state of the tissue it invades, then the degree of that disruption, captured electrically, might reflect how aggressively the disease is behaving.

The results bore out that reasoning with unusual clarity for a single-center retrospective cohort. Among the seventy-seven patients, who ranged widely in age with a mean of 55.4 years, median and mean overall survival clustered around 20.5 months, consistent with contemporary glioblastoma outcomes after maximal safe resection and standard chemoradiotherapy. On simple univariate comparisons, patients with lower IMES scores and higher CES scores died sooner. But the more important test came afterward: the researchers entered both excitability scores into Cox proportional hazards regression models alongside the classical prognostic variables, asking whether the electrical signatures still carried independent information. They did. A higher IMES was associated with a hazard ratio of 0.16, meaning substantially better survival for each increment on the score, with a p-value of 0.003. A higher CES, by contrast, carried a hazard ratio of 2.63, indicating roughly two-and-a-half-fold increased risk of death, with a p-value of 0.034.

Those numbers deserve unpacking for readers less familiar with survival statistics. In a Cox regression, a hazard ratio describes how the instantaneous risk of death changes with a one-unit increase in a given variable, holding all other variables constant. A hazard ratio below one is protective; a ratio above one is harmful. The fact that IMES and CES remained significant after adjustment for age, sex, neurological status, MGMT methylation and extent of resection means the excitability measures are not merely proxy readings of tumor size or patient fitness. They appear to encode something biologically distinct, plausibly the functional footprint of tumor infiltration into the motor network, a process that anatomical imaging and even molecular classification do not fully capture.

This interpretation fits into a fast-moving body of research on what some investigators call the onco-biological signature of brain tumors in motor systems. A landmark 2023 study in Nature showed that glioblastoma actively remodels the neural circuits it invades and that the degree of neuronal integration correlates with shortened survival, suggesting the tumor exploits neuronal activity as a trophic signal. Parallel work has documented microstructural abnormalities in the corticospinal tract and in the apparently normal white matter of the opposite hemisphere, while connectome analyses have quantified how invasion along fiber tracts predicts outcome. The nTMS excitability measures used in the London study can be understood as a functional complement to those structural metrics: rather than measuring the wiring, they measure how responsive the circuitry remains to direct stimulation.

One additional finding adds practical weight to the study. When the researchers compared excitability mapping restricted to one hemisphere against mapping that included both hemispheres, the bilateral approach improved the accuracy of twelve-month survival prediction. This detail matters biologically as well as statistically. Glioblastoma is notorious for occult crossing of midline structures such as the corpus callosum, producing so-called butterfly patterns of spread that conventional magnetic resonance imaging can underestimate. If excitability changes on the opposite, radiologically normal hemisphere carry prognostic signal, then bilateral stimulation may be sensing functional consequences of tumor infiltration that imaging alone misses, offering a cheap and repeatable window onto disease extent.

The clinical implications extend beyond prognosis into surgical decision-making. nTMS is already used in many neurosurgical centers to map motor pathways preoperatively, stratify surgical risk and plan the boundaries of resection, with a substantial literature confirming its value in reducing postoperative deficits. The new study suggests that the same data, collected routinely as part of surgical planning, could be repurposed at essentially no additional cost or burden to the patient as a prognostic tool. In an era when treatment intensification, clinical trial enrollment and even the extent of resection are calibrated to expected survival, having an objective, physiology-based biomarker available on the day of admission could meaningfully change how individualized treatment plans are drawn.

The authors and outside observers alike are careful about what the study does and does not establish. It is retrospective, comes from a single institution, and involves a modest sample of seventy-seven patients, so the hazard ratios, however compelling, require validation in independent and ideally prospective cohorts before excitability profiling enters routine practice. There are also technical considerations: motor threshold measurements can vary with coil type, limb dominance and stimulation parameters, and the field continues to debate the best standardized protocols for using motor threshold as a dependent variable in research. The King’s College team addressed methodological rigor by reporting their work in line with established guidance for prognostic marker studies and prediction models, and by adjusting for the classical covariates, but replication remains the essential next step.

Even with those caveats, the study marks a conceptual milestone in neuro-oncology. For a century, prognosis in glioma has been built from what pathologists and radiologists can see: cellular appearance, molecular markers, tumor volume and resection extent. This work adds a different dimension entirely, the living electrical behavior of the motor cortex confronting a tumor, and shows that this dimension carries information about survival that the standard battery of tests does not. If larger studies confirm the finding, the humble magnetic coil, currently valued for mapping where things are, may become equally valued for revealing how sick the system is, bringing a functional, physiologically grounded biomarker to the bedside of one of medicine’s most daunting cancers.

Subject of Research: Preoperative cortical excitability measured with navigated transcranial magnetic stimulation as a prognostic biomarker for overall survival in motor-eloquent glioblastoma

Article Title: nTMS-determined cortical excitability is associated with overall survival in patients with motor-eloquent glioblastoma

Article References: Lavrador, J. P., Mirallave-Pescador, A., Patel, S., Al-Banna, Q., Fayez, F., Prasad, V., Baig Mirza, A., Sinosi, F. A., Prakashvel, S., Rajwani, K., Kalyal, N., Chowdhury, Y. A., Marchi, F., Elhag, A., Ferrari, L., Baamonde, A. D., Mosquera, J. S., Ashkan, K., Bhangoo, R., & Vergani, F. (2026). nTMS-determined cortical excitability is associated with overall survival in patients with motor-eloquent glioblastoma. Journal of Neuro-Oncology, 179(3), Article 100. https://doi.org/10.1007/s11060-026-05806-x

Image Credits: AI Generated

DOI: 10.1007/s11060-026-05806-x

Keywords: glioblastoma, navigated transcranial magnetic stimulation, cortical excitability, overall survival, motor cortex, prognosis, brain tumor, neuro-oncology, motor mapping, biomarker, MGMT methylation, extent of resection