Rationale:
The increasing use of microelectrode recordings (MER) via depth electrodes has significantly advanced our understanding of human brain function. This progress is largely due to the development of microelectrode contacts embedded in clinical depth electrodes (e.g., Dixi Micro-Macro, Behnke-Fried, or custom-made). This technology enables recording single and multi-unit activity in addition to local field potentials along trajectories. These advances are particularly valuable in epileptic patients undergoing invasive monitoring covering widespread brain regions. Despite this opportunity, most research has focused on behavioral and cognitive processes rather than the underlying mechanisms of epilepsy. A deeper understanding of epilepsy’s neural basis is of both scientific and clinical interest. Here, we systematically review the literature on MER in epilepsy patients and identify opportunities for new research.
Methods: This review was conducted in accordance with PRISMA guidelines in multiple databases, including PubMed, EMBASE, and Google Scholar. The search strategy incorporated keywords such as “epileptic patients, depth electrodes, Behnke-Fried, microelectrode recordings, single units, multi-unit activity, action potentials, micro contacts, and seizure onset zone.” Included studies involved human epilepsy patients and employed depth electrodes equipped with microelectrode contacts.
Results: 70 studies met inclusion criteria. MERs were primarily obtained from mesial temporal structures including the hippocampus (23), amygdala (21), entorhinal cortex (8), and parahippocampal gyrus (4). Depth electrode placement was guided by clinical necessity. Of the 70 studies, 37 pursued cognitive research goals such as memory, perception, and navigation. 17 studies were clinically focused, and investigated seizure onset zone (SOZ) localization, prediction, or neuromodulation. Technical articles and reviews accounted for the remainder of studies. Across all studies, recordings were collected from a total of 1113 patients from 44 different research centers. Patient ages ranged from 12 to 70 years (mean: 37.3± 5.3). On average, 735 neurons were recorded per study. However, clinical studies recorded fewer neurons per patient (mean: 10.8± 13.4) compared to cognitive studies (mean: 53.7± 43.4) (Welch t-test, p = 0.03*). Commonly reported challenges included electrode positioning, signal stability over time, noise management, and integration of research systems into clinical workflows.
Conclusions: The existing literature on MER in epilepsy patients includes data from over 1000 individuals, with most studies focusing on cognitive processes in adults. In contrast, clinical applications and pediatric use of MER remain underexplored, highlighting key opportunities for future investigation. Future clinical research could explore the use of interictal MER for SOZ identification to reduce the need to capture spontaneous seizures; investigate neuronal firing patterns that predict ictal activity to better inform responsive neuromodulation treatment strategies; and elucidate potentially treatment-relevant mechanistic differences across neurodevelopmental stages.
Funding: This project was supported by DIXI Medical.