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Characterisation of very fast oscillations (VFOs) in human frontal cortical slices in vitro

Lookup NU author(s): Dr Michelle Pierce, Dr Anita Roopun, Dr Alistair Jenkins, Dr Ian Schofield, Professor Miles Whittington, Professor Mark Cunningham



Very fast oscillations (VFOs; 80-500Hz) are observed in the electrocorticogram of epilepsy patients, both inter-ictally and preceding seizure onset. We studied the properties of VFOs in human cortical slices in vitro to probe the mechanisms underlying this activity. Human frontal cortex was obtained from patients undergoing surgery for intractable epilepsy or tumour removal, and was categorised as ‘epileptic’ or ‘non-epileptic’ according the patient’s seizure history and to whether the resected region contained the presumed epileptic focus. Informed consent was obtained prior to surgery. Standard in vitro techniques were used to record extracellular field potentials from 450µm slices. VFOs were detected and analysed with an automated MATLAB programme. 4/74 ‘epileptic’ slices from 2/9 patients displayed spontaneous interictal-like discharges containing VFOs. VFOs were either superimposed on an accompanying sharp wave (SW) or occurred independently. The mean frequency of SW-associated VFOs was 279.4±162.2Hz (n=788 events from 2 patients), whereas that of independent VFOs was significantly lower (265.1±100.1Hz, n=803 events from 2 patients; p=0.034). 11 slices from 5 additional patients displayed similar VFOs in the presence of the kainate receptor agonist kainate (100-400nM). Like spontaneous VFOs, kainate-evoked SW-associated VFOs (n=618 events from 2 patients) were significantly faster than independent VFOs (n=1558 events from 5 patients; p<0.001); and both were significantly higher in frequency than their spontaneous counterparts (321.1±172.1Hz and 294.4±129.5Hz respectively; p<0.0001). Rarely (1/52 slices from 12 patients), spontaneous independent VFO was observed in non-epileptic tissue (293.9±107.9Hz, n=226 events). Additionally, kainate induced SW-associated (1 slice, 100nM kainate) and independent (2 slices from 2 patients, 600-700nM kainate) VFOs in a few non-epileptic slices. Intracellular sharp electrode recording from lamina III of an epileptic slice revealed compound EPSPs in a fast-spiking interneurone occurring synchronously with SW-associated VFOs in the nearby field. High-pass filtering revealed a fast component to the compound EPSPs at the same frequency as the field VFO. This fast component was 180° out-of-phase with the field and the peak of each component lagged the negative-going peak of the field potential by a median of 2.7ms (IQ range=1.8-4.1ms). In conclusion, VFOs (spontaneous or kainate-induced) are present in a higher proportion of epileptic (7/9) than non-epileptic (4/12) human frontal cortical preparations. SW-associated and independent VFOs had distinct frequencies, suggesting differences in their mechanism of generation. SW-associated VFOs, at least, may be accompanied by phase-locked excitatory inputs to local interneurones, but these inputs do not appear to be a causal factor in VFO generation.

Publication metadata

Author(s): Pierce ML, Roopun AK, Crossman JE, Jenkins A, Schofield IS, Whittington MA, Cunningham MO

Publication type: Conference Proceedings (inc. Abstract)

Publication status: Published

Conference Name: Annual Meeting of the International League Against Epilepsy (UK Chapter)

Year of Conference: 2009

Date deposited: 05/08/2010

Publisher: International League Against Epilepsy