Matsumoto A, Brinkmann BH, Stead SM, Matsumoto J, Kucewicz MT, Marsh WR, Meyer F, Worrell G. Pathological and physiological high-frequency oscillations in focal human epilepsy. J Neurophysiol 110: 1958 -1964. First published August 7, 2013 doi:10.1152/jn.00341.2013.-High-frequency oscillations (HFO; gamma: 40 -100 Hz, ripples: 100 -200 Hz, and fast ripples: 250 -500 Hz) have been widely studied in health and disease. These phenomena may serve as biomarkers for epileptic brain; however, a means of differentiating between pathological and normal physiological HFO is essential. We categorized task-induced physiological HFO during periods of HFO induced by a visual or motor task by measuring frequency, duration, and spectral amplitude of each event in single trial time-frequency spectra and compared them to pathological HFO similarly measured. Pathological HFO had higher mean spectral amplitude, longer mean duration, and lower mean frequency than physiological-induced HFO. In individual patients, support vector machine analysis correctly classified pathological HFO with sensitivities ranging from 70 -98% and specificities Ͼ90% in all but one patient. In this patient, infrequent high-amplitude HFO were observed in the motor cortex just before movement onset in the motor task. This finding raises the possibility that in epileptic brain physiological-induced gamma can assume higher spectral amplitudes similar to those seen in pathologic HFO. This method if automated and validated could provide a step towards differentiating physiological HFO from pathological HFO and improving localization of epileptogenic brain.high-frequency oscillations; epilepsy; gamma oscillations HIGH-FREQUENCY OSCILLATIONS (HFO) have been widely studied in animals and humans and linked to brain function in health and disease (Buzsaki and Silva 2012). Physiological highfrequency gamma oscillations (gamma: ϳ40 -100 Hz) are believed to coordinate cortical processing during vision (Gray and Singer 1989), motor, and language functions (Crone et al. 2011). Physiological hippocampal high-frequency oscillations (ripples: 100 -200 Hz) are thought to play an important role in memory functions (Buzsaki et al. 1992).Pathological HFO (pHFO) were initially observed in hippocampal recordings from epileptic rats and thought to be a specific electrophysiological biomarker of epileptic tissue (Bragin et al. 1999b). The pHFO observed in epileptic rats included fast ripples (250 -500 Hz) that colocalize to the epileptic hippocampus-generating seizures in rats (Bragin 1999b(Bragin , 2002 and humans (Bragin 1999a). In addition, ripple HFO were observed in the hippocampal dentate gyrus of epileptic rats but not in control rats and were therefore considered pHFO (Bragin 2002). The cellular correlates of normal physiological hippocampal ripples were shown to be inhibitory postsynaptic potentials (Ylinen et. al. 1995) and pathological fast ripples were shown to be synchronous population firing of large groups of pyramidal cells and decreased inhibitory interneuron firin...

Eleven patients being evaluated with intracranial electroencephalography for medically resistant temporal lobe epilepsy participated in a visual recognition memory task. Interictal epileptiform spikes were manually marked and their rate of occurrence compared between baseline and three 2 s periods spanning a 6 s viewing period. During successful, but not unsuccessful, encoding of the images there was a significant reduction in interictal epileptiform spike rate in the amygdala, hippocampus, and temporal cortex. During the earliest encoding period (0-2000 ms after image presentation) in these trials there was a widespread decrease in the power of theta, alpha and beta band local field potential oscillations that coincided with emergent focal gamma frequency activity. Interictal epileptiform spike rate correlated with spectral band power changes and broadband (4-150 Hz) desynchronization, which predicted significant reduction in interictal epileptiform spike rate. Spike-triggered averaging of the field potential power spectrum detected a burst of low frequency synchronization 200 ms before the interictal epileptiform spikes that arose during this period of encoding. We conclude that interictal epileptiform spikes are modulated by the patterns of network oscillatory activity that accompany human memory offering a new mechanistic insight into the interplay of cognitive processing, local field potential dynamics and interictal epileptiform spike generation.

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