['The objective of our study was to determine noninvasively whether metabolic dysfunction is present in focal areas of interictal electrophysiologic abnormality and whether metabolic dysfunction correlates with frequency of spiking.', 'We used a prospective, power analysis-driven, age-matched design to study 20 subjects with nonlesional temporal lobe epilepsy by using magnetoencephalography (MEG) and proton magnetic resonance spectroscopy (1H-MRS). MEG was used to localize the source area of interictal spikes. 1H-MRS measured integrated peak areas for N-acetyl compounds (NAA) and choline-containing compounds (Cho) in both hippocampi, the MEG spike zone, and the region contralateral to the MEG spike zone in all subjects. 1H-MRS was performed in seven controls.', 'Fifteen of 20 subjects had a lower NAA/Cho ratio in the MEG spike zone compared with the contralateral homologous region. NAA/Cho was significantly decreased in the MEG spike zone (p < 0.01). NAA/Cho ratios were not significantly different between the hippocampus ipsilateral and contralateral to the spike activity, or from control hippocampi. NAA/Cho ratios did not correlate with spike frequency.'] Are areas of interictal spiking associated with metabolic dysfunction in MRI-negative temporal lobe epilepsy?