Multi-site Stimulation for Controlling Bursting in Cortical Ensembles
NIH Workshop on Neural Interfaces, Bethesda, MD, Nov 15–17, 2004
We developed a device that can deliver arbitrary stimulation sequences to each of 60 electrodes in an in vitro neural interface (MEA). We have used this system to control bursting in ensembles of cortical neurons in high-density dissociated culture. The spontaneous activity of such ensembles is characterized by bursts globally synchronized across the entire culture. These recur at intervals ranging from seconds to a minute, alternating with periods of sparse firing. Single stimuli applied at low frequencies (below 0.2 Hz) typically entrain bursts. We found that the very same stimuli can be combined to reduce or even abolish bursting by increasing the stimulation rate to 10-50 Hz, and distributing the stimuli across up to 25 electrodes. Moreover, we found that a stimulation protocol that explicitly controls tonic firing rates using real-time closed-loop feedback effectively abolished bursting in 50% of cultures using only 10 electrodes. While good burst control was observed in several cases using single electrodes, we found that the use of multiple electrodes greatly increased the reliability of the technique. Perfect burst suppression was achieved by delivering 50 stimuli/s distributed across 25 electrodes.
Our stimulator hardware could easily be adapted for use with in-vivo neural interfaces. We hope that burst control by multi-site stimulation may find application in clinical approaches to the reduction of epileptic seizures by focal stimulation.