Nevalainen, P. | bioRxiv Science

bioRxiv2026

A novel method for obtaining epileptic brain tissue for omic analyses using electrodes from a clinical stereoelectroencephalography study

Abstract Purpose: Developing a valid and practical method for obtaining brain tissue samples for transcriptomic and proteomic analyses using tissue adhered to stereoelectroencephalography (SEEG) electrodes, to enable investigation of the molecular mechanisms underlying chronic epilepsy. Method: Brain tissue samples adhered to SEEG electrodes were collected from six patients with drug-resistant epilepsy and preprocessed in a hospital environment after electrode removal. RNA extraction was initiated immediately, and proteomics samples were snap-frozen until subsequent analysis. The samples were categorized into three groups according to their electrophysiological profile: epileptogenic zone, propagation zone, and least-involved zone. The omic findings between these zones and anatomical brain areas were compared. Results: High-quality RNA and protein samples were obtained from tissue adhered to SEEG electrodes. Neuron- and brain-specific gene expression patterns and proteins were identified. Signs of activation of inflammatory mechanisms were most pronounced in the epileptogenic zone. Transcriptomic and proteomic findings demonstrated concordance. Conclusion: SEEG electrodes are a useful source for obtaining brain tissue for molecular characterization of chronic epilepsy. This method will enable the identification of shared and distinct molecular mechanisms in patients with varying etiologies of epilepsy.

neuroscience↗

bioRxiv2025

Directed cortico-limbic dialogue in the human brain

How can one trace the brains orderly directed signals amid a tangle of nerve fibers? Because direct access to actual brain signaling is rare in humans, the precise wiring diagrams for cortico-limbic communication during sleep and wake remain essentially unmapped, hampering progress in neuroscience. Now, a unique neurosurgical window on the human brain allows for electrically mapping cortical connections at the hospital, but studies so far have relied on average signals, masking the dynamic nature of signal flow across brain regions. To causally estimate signaling dynamics, we repeatedly probed cortico-limbic networks with short-lived electrical pulses over days and assessed the variable fate of each transmitted signal on a single-trial basis. In the resulting openly available dataset, we characterized signaling probabilities and directionality across thousands local and long-range cortico-limbic connections over days. Challenging established views, we found that limbic structures send twice as many signals as they receive, in both wakefulness and sleep. Our findings provide a fundamental framework for causally interpreting signal flow in the brain and formulating therapeutic strategies for brain networks disorders.

neuroscience↗