Safety of Subdural Direct Current Stimulation: A Histological Study in the Ovine Brain Using Metal Electrodes

Area of Science:

• Neuroscience
• Biomedical Engineering
• Neuromodulation

Background:

• Direct current (DC) stimulation offers unique neuronal modulation compared to pulsatile methods.
• Intracranial DC use is limited by potential tissue damage at the electrode-brain interface.
• Quantitative safety limits for intracranial DC stimulation are not well-defined.

Purpose of the Study:

• To establish histological safety boundaries for direct cortical DC stimulation using metal electrodes.
• To investigate the relationship between stimulation parameters and tissue damage in a large-animal model.

Main Methods:

• Cathodal DC stimulation applied to sheep cortex using clinical-grade electrodes.
• Varied current densities (0.7 to 144.4 mC/mm²) delivered for 10-15 minutes.
• Histological examination of brain tissue for damage and quantification of lesion volumes.

Main Results:

• No lesions observed below 0.7 mC/mm² charge density.
• Lesion probability and volume increased with charge density, showing significant variability.
• Estimated zero-lesion threshold ranged from 2.3 mC/mm² (linear regression) to 8.7 mC/mm² (nonlinear models).

Conclusions:

• Safe application of direct cortical DC stimulation is feasible within specific parameter constraints (current, duration, electrode size).
• Findings provide quantitative guidance for safe DC neuromodulation in research and clinical settings.
• This study addresses critical safety data for advancing DC brain stimulation techniques.