Abstracts

Rationale: Subdural hybrid neuroprosthetic devices were recently proposed for the treatment of intractable focal seizures (Ludvig et al., 2006; Epilepsia 47:1792-1802). These devices will need a reliable seizure prediction method. Such a method may use not only EEG waves but various other brain signals, as well. Neocortical multi-neuron activity is one of these potentially useful, non-EEG signals from the brain. Indeed, it has been demonstrated that in the rat hippocampus neuronal firing rate increases precede local EEG seizures (Ludvig and Tang; 2000; Brain Res. Bull. 51:233-240). The present study was designed to test whether changes in multi-neuron activity also precede focal neocortical seizures in this species. Methods: Rats were chronically implanted with an epidural cup placed over the right parietal cortex, with eight parallel microelectrodes (50 micrometer diameter each) introduced into the underlying cortical tissue, approx. 1 mm below the center of the exposed dura mater. Importantly, the microelectrodes were introduced into the parietal cortex from a penetration site outside of the epidural cup, in a 7 degree angle, leaving the exposed dura intact. Similar microelectrodes were also implanted in the temporal muscle. After a postsurgical recovery period, both local EEG activity (using a band-pass of 0.1 – 500 Hz) and multi-neuron activity (using a band-pass of 300 – 10,000 Hz), as well as EMG activity, were recorded, while the rat was behaving freely. Digital video cameras monitored the animal’s behavior. After the collection of 5 - 10 min control (pre-seizure) data, acetylcholine (34 - 68 mM; pH = 7.4; 50 microliter volume) was delivered into the cup to induce focal seizures. Software by DataWave Technologies was used to analyze the neuronal, EEG and EMG data. Results: EEG seizures developed within 1 minute after the epidural delivery of acetylcholine. The paroxysmal EEG activities were not accompanied with convulsions, since in these experiments relatively low concentrations of acetylcholine were applied to induce limited focal seizures. Approximately 20 seconds prior to the first EEG spikes, increased multi-neuron activity was recorded, which was often followed by the temporary cessation of neuronal discharges. As the EEG seizures developed, the paroxysmal EEG spikes and spike-and-waves were accompanied with simultaneous bursts in the multi-neuron recording channels. EMG activity could be distinguished from both EEG and multi-neuron activity. Conclusions: This study suggests that neocortical multi-neuron recording can yield useful information for predicting the onset of an imminent local EEG seizure. The challenge is to make this recording technique suitable for long-term data collection with low power requirements and with microelectrodes that cause no harmful tissue damage. (Supported by NYU/FACES.)