Electrical stimulation of the septal nuclei via deep brain stimulating
electrodes is proposed as a potentially beneficial
therapy for medication-resistant
temporal lobe epilepsy. In a multicenter study, stimulation of anterior thalamus was shown to reduce numbers of
seizures, but decrease was only in the range of 40%. This might be improved with septal stimulation, which has strong and direct reciprocal connections with the hippocampal formation, the structure most involved in
temporal lobe epilepsy. Medial septal neurons drive a 3-12 Hz theta rhythm in hippocampus of rodents. Theta rhythm is less obvious in human hippocampus, but it is present and it varies with cognitive tasks. The hippocampal theta rhythm is disrupted by
seizures. In animal models, restoration of theta by sensory stimulation, septal electrical stimulation or
cholinergic drugs infused into septum ameliorates
seizures. Seizure activity in hippocampus is faithfully reflected in septal nuclei, and septum sometimes leads the seizure activity. A subset of patients with
temporal lobe epilepsy have structural enlargement of their septal nuclei. At high levels of intensity, septal stimulation is subjectively pleasurable and strongly reinforcing. Rats will repeatedly press a bar to stimulate their septum. Initial experience with human septal stimulation in the 1950s was not favorable, with ineffective
therapy for
schizophrenia and a high rate of surgical complications. Subsequent experience in 50-100
pain patients employing modern neurosurgical techniques was more favorable and demonstrated septal stimulation to be safe and tolerable. The current state of knowledge is sufficient to consider design of a clinical trial of medial septal stimulation in selected patients with medication-resistant
temporal lobe epilepsy.