Neurosurgical Patients as Human Research Subjects: Ethical Considerations in Intracranial Electrophysiology Research

Abstract

Intracranial electrical recordings and stimulation of neurosurgical patients have been central to the advancement of human neuroscience. The use of these methods has rapidly expanded over the last decade due to theoretical and technical advances, as well as the growing number of neurosurgical patients undergoing functional procedures for indications such as epilepsy, tumor resection, and movement disorders. These methods pose the potential for ethical conflict, as they involve basic neuroscientific research utilizing invasive procedures in human patients undergoing treatment for neurological illnesses. This review addresses technical aspects, clinical contexts, and issues of ethical concern, utilizing a framework that is informed by, but also departs from, existing bioethical literature on matters in clinical research. We conclude with proposals for improving informed consent processes to address potential problems specific to intracranial electrophysiology research, a general schema for scrutinizing research-related risk associated with different methods, and a call for the development of consensus to ensure continuing scientific progress alongside crucial patient protections in this promising area of human neuroscience.

FIGURE 1.

Spatial and temporal resolution. Comparison of spatial and temporal resolution of prevailing invasive methods in human neurophysiology (ECoG, electrocorticography; sEEG, stereotactic electroencephalography) to alternatives such as EEG, MEG, and functional MRI (fMRI). In dashed blue outline, “microECoG” represents ongoing development of higher-density recording techniques.

FIGURE 2.

Expansion of intracranial electrophysiology research, 1950-2014. Plotted in bars against the right axis are PubMed references for human research utilizing electrocorticography (ECoG) and stereotactic electroencephalography (sEEG). For trend comparison, plotted as lines against the left axis at 40:1 scale are references for 2 established noninvasive human neuroscience methods, EEG (subtracting out references for ECoG and sEEG) and functional MRI (fMRI).

FIGURE 3.

Techniques for intracranial electrode placement. A, Reconstruction of postoperative image from epilepsy patient undergoing electrode placement, illustrating placement of electrocorticography grid (depicted in red), electrocorticography strip (depicted in blue, extending outside craniotomy margin), and penetrating depth electrode (depicted in green). B, Volumetric MRI slice from the same patient demonstrating the location of the depth electrode probe (contacts depicted in green). Other techniques not depicted include stereotactic electroencephalography and microelectrode recording for deep brain stimulation using burr holes rather than craniotomy.

FIGURE 4.

Two dimensions of ethical scrutiny.