Microscale Electrophysiological Markers May Help in the Development Antiseizure Therapies
Key findings
- In this study, microelectrodes with 50-micron spatial resolution were used to record neural activity during neurosurgery in 30 patients
- The recordings were able to track interictal discharges, which could either involve relatively large areas of cortex or be localized to regions as small as 50 microns, and which could propagate through multiple identifiable paths over the cortical surface
- High-frequency oscillations detected by the microelectrodes demonstrated localized clustering on the cortical surface
- In two patients, the recordings revealed microseizure events that were primarily localized to single contacts, with notable voltage spread to neighboring contacts, further illustrating the distinctly local nature of epileptic events
- Future research at microscale is expected to better characterize the epileptic network and facilitate the development of therapies to modulate or interrupt it
"Microseizures" have been reported as a form of epileptiform activity that may indicate the seizure onset zone. Like interictal discharges and high-frequency oscillations, microseizures have been described on the scale of millimeters to centimeters, but the lower spatial limit is unknown.
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Advanced organic material called poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) allows the manufacture of micron-level, high spatial resolution electrodes that can examine highly localized phenomena. Using PEDOT:PSS microelectrodes with 50-micron spatial resolution, Jimmy C. Yang, MD, neurosurgery resident, and Sydney Cash, MD, PhD, co-director of the Center for Neurotechnology and Neurorecovery (CNTR) of the Department of Neurology at Massachusetts General Hospital, and colleagues have observed that local microdomains can demonstrate epileptiform activity.
In Clinical Neurophysiology, they say these results could help uncover mechanisms underlying epilepsy, inform neurosurgical decisions and facilitate the development of therapies that modulate or interrupt the epileptic network.
Study Methods
The recordings were performed in 30 patients, average age 40, while they were undergoing a neurosurgical procedure at Mass General or Brigham and Women's Hospital. For 22 patients, the procedure was related to epilepsy; seven were having a tumor resected and one had vascular malformation resection.
Interictal Discharges (IIDs)
Recordings from three patients could not be analyzed because of substantial movement artifacts. For the other patients, IIDs could be divided into two types:
- General—occurred over more than 50% of the electrode array (93% of patients)
- Local—appeared on fewer than 50% of the channels (53% of patients)
The researchers found evidence that general IIDs travel across the cortical surface. For each participant, they saw at least two paths clustered across IIDs and often many more (average, 10 paths). This suggests an underlying epileptic network that promotes an IID progression across the cortex that is unique to each individual.
High-frequency Oscillations
Three additional recordings had to be excluded because of electrical noise, probably caused by the intraoperative environment. In all 24 remaining recordings, fast-ripple high-frequency oscillations were detected over the cortical surface in unique, repeatable patterns.
Periodic Patterns and Microseizures
Repeating IIDs appeared in a few electrodes in two patients. The smallest distance involved was 50 microns. There was no significant evolution or spread, so these were considered periodic patterns rather than distinct seizure events.
Microseizure events were noted in two participants. Localized epileptiform discharges were seen primarily on one electrode and spread to the neighboring electrode contact, spanning 100 microns in one participant and 50 microns in the other. These events did not clinically manifest intraoperatively.
Conclusions
Using the microelectrodes, it was possible to evaluate the anatomy of epileptiform activity at a microscale. This approach has substantial implications for understanding the basic physiology of epilepsy; how to detect, track and localize pathological activity; and how to develop novel seizure control therapies that focus on microdomains of epileptiform neural action.
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