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Noninvasive Measurement of Brain Activity Might Improve Prognostication, Treatment of Glioma

Key findings

  • Previous laboratory experiments have shown that increased activity of neurons surrounding glioma tissue significantly enhances tumor growth
  • Neuroligin-3 (NLGN3), a synaptic protein secreted through neuronal activity, has been proposed to be a key contributor to this process
  • Lower oscillatory brain activity, measured by magnetoencephalography, was associated with lower expression of NLGN3 in a cohort of 24 patients with newly diagnosed diffuse glioma
  • Lower oscillatory brain activity predicted longer progression-free survival in the cohort
  • Oscillatory brain activity could be useful in prognostication and to monitor glioma growth, and global brain activity might be a feasible treatment target

Most gliomas in adults are diffuse, in that tumor cells broadly infiltrate the surrounding brain tissue. Diffuse gliomas are likely to impair neurophysiological functioning, potentially leading to poorer cognitive performance and epileptic seizures.

Evidence is emerging of a reciprocal relationship between altered neurophysiological functioning and glioma. Laboratory experiments have shown that increased activity of neurons surrounding glioma significantly enhances tumor growth. NLGN3 secretion is linked to neuronal activity and cancer growth. In animal experiments, blocking NLGN3 resulted in reduced glioma growth.

Linda Douw, PhD, of the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital, and colleagues in Amsterdam recently became the first to conduct a clinical study of neuronal activity, NLGN3 expression and glioma progression. Their findings, published in The Journal of Neuro-Oncology, suggest that noninvasive measurement of brain activity could improve prognostication for patients with glioma and perhaps even lead to new therapeutic strategies.

Dr. Douw and her colleagues studied 24 adults who were confirmed to have diffuse glioma and presented to a brain tumor center in Amsterdam between 2010 and 2012. The patients were in relatively good condition: the average age was 39, all but one patient had a Karnofsky performance status ≥80 and 16 patients had World Health Organization (WHO) grade II glioma. Of the others, six had grade III glioma and two had glioblastoma (astrocytoma, WHO grade IV).

The patients underwent magnetoencephalography, a noninvasive technique that measures oscillatory brain activity. All patients then underwent surgery. Resected glioma tissue, if available, was used to measure the expression of NLGN3.

Level of Oscillatory Brain Activity

Of the 21 patients who had resected tissue available, 12 were classified as having low expression of NLGN3, six had moderate expression and three had high expression. Oscillatory brain activity varied significantly according to the level of NLGN3 expression, not just in the peritumor region but globally throughout the brain. Patients with the lowest NLGN3 expression showed the lowest global brain activity.

The median progression-free survival (PFS) in the cohort was 87 weeks. On univariate analysis, lower levels of oscillatory brain activity were associated with longer PFS in all areas of the brain:

  • Peritumor area: (HR, 2.17; 95% CI, 1.23–3.85; P = .008)
  • Globally (HR, 2.10; 95% CI, 1.22–3.63; P = .008)
  • Non-tumor areas of the brain (HR, 2.05; 95% CI, 1.18–3.58; P = .01)

Brain activity was a significant predictor of PFS in all analyses even after adjustment for numerous confounding variables, including age, gender, performance status, tumor grade, tumor histology, tumor size, IDH1 mutation status, a potential prognostic confounder, and type of adjuvant treatment.

Interplay Between Brain Activity and Glioma Progression

The researchers conclude that measuring oscillatory brain activity could be clinically useful in the context of glioma, for instance, to monitor tumor growth. They also propose that global brain activity might be a feasible treatment target in glioma, perhaps in addition to inhibition of NLGN3 secretion. As an example, the authors point out that anti-epileptic drugs reduce neuronal activity, and several studies have shown that they improve survival in glioblastoma.

Learn more about the Athinoula A. Martinos Center for Biomedical Imaging

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