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

## TL;DR

The Freiburg framework is a new method to study human brain tissue in a lab setting using multiple techniques to understand brain function and variability.

## Contribution

The Freiburg framework introduces a structured multimodal approach for ex situ human cortical tissue assessment integrating electrophysiology, imaging, molecular analyses, and Raman microscopy.

## Key findings

- The framework combines high-resolution electrophysiology, imaging, molecular analyses, and Raman microscopy for assessing neuronal and glial function.
- It incorporates clinical metadata and in-patient controls to account for biological variability and enable human-to-human translational comparisons.
- The framework allows controlled neuromodulatory and pharmacological interventions, including ex situ repetitive transcranial magnetic stimulation (rTMS).

## Abstract

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 ex situ 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 ex situ 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.