7. Identifying the pathological substrate(s) of complex partial seizures: Blumenfeld’s network inhibition hypothesis

Abstract

Complex partial seizures – which often arise in the temporal lobes – are the most common seizures in adults and are often drug resistant. They involve transient episodes of impaired consciousness with behavioural arrest. Identifying the neural substrate for these common and drug-resistant attacks will be valuable not only for understanding epileptogenic networks, but also for evolving new pharmacologic or stimulation paradigms designed for complex partial seizures. Dr. Hal Blumenfeld at Yale University has offered a testable hypothesis concerning the neural substrate of complex partial seizures. Blumenfeld postulates (2012) : (1) that focal discharge arises somewhere in the brain, typically in the temporal lobes; (2) that the focal discharge spreads to subcortical structures that have strong inhibitory outputs, such as the septal nuclei; and (3) that the discharge in these structures suppresses activity in the arousal systems of the upper brain stem and diencephalon. Suppression of the arousal systems leads to unconsciousness, which is signaled by the onset of behavioural arrest and slow waves in the neocortical EEG. Blumenfeld’s hypothesis has not yet been tested in the amygdala-kindling model – the most widely used and drug-validated animal model of complex partial seizures. Tests involving the Blumenfeld hypothesis and amygdala-kindled rats are now underway in our laboratory. We predict that behavioural arrest in kindled animals will correlate with the onset of slow waves in the rat neocortex. We also predict that the behavioural arrest will not be suppressed by anti-epileptic drugs (AEDs), since AEDs do not suppress complex partial seizures in patients or the kindled amygdala focus in rats ( Albright and Burnham, 1980 ).