The Freiburg framework for multimodal ex situ assessment of neural plasticity in human cortical tissue

Studying human cortical physiology requires access to viable brain tissue, yet species-specific differences limit the translational value of animal models. To address this, multiple laboratories have developed <i>ex situ</i> approaches for investigating neurosurgical access tissue using electrophysiological, molecular, and imaging techniques. Here, we introduce the Freiburg framework-a structured, multimodal approach that integrates high-resolution electrophysiology, advanced imaging, molecular analyses, and Raman microscopy to assess neuronal and glial function under controlled, near-native conditions. Clinical metadata, including preoperative MRI, together with in-patient controls is systematically incorporated to account for biological variability and to enable human-to-human translational (H2H) comparisons. The framework further enables controlled neuromodulatory and pharmacological interventions, including <i>ex situ</i> repetitive transcranial magnetic stimulation (rTMS). By formalizing an end-to-end experimental pipeline, the Freiburg framework supports systematic investigation of human-specific neurophysiological mechanisms and provides a robust foundation for translational human neuroscience.