Prediction error connectivity: A new method for EEG state analysis.

Several models have been proposed to explain brain regional and interregional communication, the majority of them using methods that tap the frequency domain, like spectral coherence. Considering brain interareal communication as binary interactions, we describe a novel method devised to predict dynamics and thus highlight abrupt changes marked by unpredictability. Based on a variable-order Markov model algorithm developed in-house for data compression, the prediction error connectivity (PEC) estimates network transitions by calculating error matrices (EMs). We analysed 20 h of EEG signals of virtual networks generated with a neural mass model. Subnetworks changed through time (2 of 5 signals), from normal to normal or pathological states. PEC was superior to spectral coherence in detecting all considered transitions, especially in broad and ripple bands. Subsequently, EMs of real data were classified using a support vector machine in order to capture the transition from interictal to preictal state and calculate seizure risk. A single seizure was randomly selected for training. Through this approach it was possible to establish a threshold that the calculated risk consistently overcame minutes before the events. Using either spectral coherence or PEC we created 1000 models that successfully predicted 6 seizures (100% sensibility), a whole cluster recorded in a patient with hippocampal epilepsy. However, PEC resulted superior to coherence in terms of true seizure free time and amount of false warnings. Indeed, the best PEC model predicted 96% of interictal time (vs. 83% of coherence) of about 20 h of stereo-EEG. This analysis was extended to patients with neo/mesocortical temporal, neocortical frontal, parietal and occipital lobe epilepsy. Again PEC showed high performance, allowing the prediction of 31 events distributed across 10 days with ROC AUCs that reached 98% (average 93 ± 5%) in 6 different patients. Moreover, considering another state transition, PEC could classify and forecast up to 88% (average 85 ± 3%) of the REM phase both in deep and scalp EEG. In conclusion, PEC is a novel approach that relies on pattern analysis in the time-domain. We believe that this method can be successfully employed both for the study of brain connectivity, and also implemented in real-life solutions for seizure detection and prediction.