“The bottom line is that seizures in which stimulation is not effective are ones that are likely more evolved or perhaps began in a different place in the network and spread to these regions before the stimulation occurred,” he said.
Although Dr. Litt's model for seizure generation has not been statistically proven, his group's research suggests that seizures “may occur in a reproducible cascade of events” in which there are periods of increased complex epileptiform activity in the hours or days before a seizure, followed in the 2 hours before the seizure by short seizurelike bursts of activity, or “seizlets,” that last 1–5 seconds. These seizlets appear to build exponentially as the seizure approaches and activity ramps up.
To prove that this cascade of events exists, the investigators have built detectors that can quantitatively detect seizures in large chunks of data. When seizure and nonseizure events are mixed up and randomized, the two events can be distinguished with a certain latency, which increases as the likelihood of correctly predicting a seizure event increases, he said.
Other investigators who have collaborated with Dr. Litt may have come across a good method for validating the performance of algorithms that are designed to predict seizures.
This method also may have discovered the first evidence for the EEG patterns of a definitive preictal period (J. Neurophysiol. 2006 Oct. 4 [Epub DOI:10.1152/jn.00190.2006]).
Pinpointing the location of seizures has benefited from research using high-frequency EEG.
High-frequency EEG readings were not recognized as clinically significant until recent studies showed that the characteristic waveform flattening, or “electro-decrement,” of intracranial EEG before a seizure is actually high-frequency activity that was filtered out by intracranial EEGs that were calibrated to filter settings of pen and paper EEG machines from the 1950s, Dr. Litt said.
For many seizures, a rise in high-frequency epileptiform oscillations can indicate an impending seizure 40 minutes in advance (Brain 2004;127:1496–506).
Investigations of the density of these high-frequency epileptiform oscillations during a period of time around specific electrodes in the brain have helped to map the distribution of nodes that are “heating up” before seizure onset, he explained.
These maps have suggested that the focal point of a seizure is not really like a single point, as was previously thought, but is “more like a cloud. It's areas that are buzzing and trying to initiate synchrony that seem to be going from one place to the other to generate the seizure, and which ones actually start the seizure may vary,” he said.