Abstracts

Rationale: Hypothalamic hamartomas (HH) are rare congenital tumors occurring in the ventral hypothalamus. HH are intrinsically epileptogenic, but the basic cellular mechanisms responsible for seizure generation are unknown. Prior studies of surgically-resected HH tissue slices have shown that the small HH neurons possess intrinsic pacemaker-like firing. We sought to determine if such firing is present in situ, prior to the disruption of network connections by resection. Methods: We recorded extracellular potentials reflecting single neuron activity from bundles of 9 microwires (38 ?m diameter) inserted through a surgical endoscope into the HH prior to resection (Lekovic GP, et al., Neurosurgery, 2009). Extracellular potentials were sampled at 29412 Hz and bandpass filtered (300-3000 Hz). Filter output was examined for single unit spike activity, with analysis of 1.1 millisecond (ms) epochs surrounding the time of voltage extrema (>2.8 channel s.d.). These were isolated and sorted into spike clusters of similar waveform shape using a Classification Expectation-Maximization (CEM) clustering algorithm. Results: We recorded in situ single unit activity from 11 patients (mean age 14.6 years ,range 2.2-34.1 years; 7 females, 64%), under anesthesia with sevoflurane. In total we recorded spontaneous firing from 222 neurons. The mean firing rates of these neurons segregated into two groups (figure 1), one with a low firing rate (FR) of 1.3 spikes/second, and a second group with a higher FR of 15.2 spike/second (Hartigan-Hartigan dip test for more than one mode, p<0.00001). The burst ratio (BR = fraction of inter-spike intervals < 10 ms divided by fraction of inter-spike intervals > 10 ms) also showed a strongly bimodal distribution (mode 1 = 0.022, mode 2 = 0.18; p<0.00001). Conclusions: These results demonstrate that in situ spontaneous firing rates of HH neurons (under conditions of anesthesia with halogenated gases) segregate into two groups. The higher firing rate observed here is similar to firing rates previously reported for small HH neurons in acutely dissociated single-cell preparations (10.5 /- 0.8 Hz) (Wu J, et al., Ann Neurol, 2005) and freshly-resected HH tissue slices (6.6 /- 1.0 Hz) (Kim DY, et al., Epilepsia, 2008). A subgroup of HH neurons fire spontaneously even when all network connections are preserved in the intact brain.