Abstracts

Rationale: Human hypothalamic hamartomas (HH) are intrinsically epileptogenic for treatment-resistant galactic seizures. However, the basic cellular mechanisms responsible for the epileptogenicity of HH tissue are unknown. Microelectrode patch-clamp recordings from HH neurons in resected slice preparations show that small HH neurons demonstrate intrinsic pacemaker-like activity. We hypothesized that spontaneous firing of single neurons is present in-situ, and that microwire recordings in HH tissue prior to surgical resection would demonstrate firing behavior consistent with a functional network. Methods: Patients undergoing transventricular endoscopic resection of HH for treatment-resistant epilepsy were included. Single neuron recordings from bundled microwires (total of 9 contacts) were obtained from HH tissue immediately prior to surgical resection in 14 patients. Spontaneous activity was recorded for two or three 5-minute epochs under steady-state general anesthesia. Off-line analysis included cluster analysis of single neuron activity, and probability analysis of firing relationships between different neurons. Results: A total of 222 neurons were identified in 14 patients (mean 6 neurons per recording epoch). Cluster analysis of single neuron behavior identified two distinct populations on the basis of mean firing rate (FR) and burst density (Bisi = # interspike intervals>10 ms / # interspike intervals<10 ms) : 1. A Low FR group with median FR=0.85 spikes/s and median Bisi=0.018, and 2: A High FR group with median 16.3 spikes/s, median Bisi=0.19. Analysis of spontaneous firing behavior between single neurons showed that 417 of 813 pairs of neurons (51%) had a significant (p<0.05) degree of cross-correlation within +-2 ms of zero delay. Pairs of High FR neurons were significantly (p<0.001) more likely to be correlated. Conclusions: HH tissue in situ contains neurons with are spontaneously active. The activity of single neurons is diverse but distributes into at least two electrophysiological phenoytpes. Synchronous firing between pairs of neurons suggests that HH neurons exist within local networks that may contribute to epileptogenic firing.