Quantitative Analysis of High-Frequency Oscillations (80–500 Hz)
Recorded in Human Epileptic Hippocampus and Entorhinal Cortex
RICHARD J. STABA,
1
CHARLES L. WILSON,
2,4
ANATOL BRAGIN,
2,4
ITZHAK FRIED,
3,4
AND
JEROME ENGEL, JR
1,2,4
Departments of
1
Neurobiology,
2
Neurology, and
3
Neurosurgery and
4
The Brain Research Institute, David Geffen School of
Medicine at UCLA, Los Angeles, California 90095
Received 1 May 2002; accepted in final form 25 June 2002
Staba, Richard J., Charles L. Wilson, Anatol Bragin, Itzhak
Fried, and Jerome Engel, Jr. Quantitative analysis of high-fre-
quency oscillations (80–500 Hz) recorded in human epileptic hip-
pocampus and entorhinal cortex. J Neurophysiol 88: 1743–1752,
2002; 10.1152/jn.00322.2002. High-frequency oscillations (100–200
Hz), termed ripples, have been identified in hippocampal (Hip) and
entorhinal cortical (EC) areas of rodents and humans. In contrast,
higher-frequency oscillations (250–500 Hz), termed fast ripples (FR),
have been described in seizure-generating limbic areas of rodents
made epileptic by intrahippocampal injection of kainic acid and
observed in humans ipsilateral to areas of seizure initiation. However,
quantitative studies supporting the existence of two spectrally distinct
oscillatory events have not been carried out in humans nor has the
preferential appearance of FR within seizure generating areas received
statistical evaluation based on analysis of a large sample of oscillatory
events. Interictal oscillations within the bandwidth of 80–500 Hz were
detected in Hip and EC areas of patients with mesial temporal lobe
epilepsy using wideband EEG recorded during non-rapid eye-move-
ment sleep from chronically implanted depth electrodes. Power spec-
tral analysis showed that oscillations detected from Hip and EC areas
were composed of two spectrally distinct groups. The lower-fre-
quency ripple group was defined by a frequency of 96 ⫾ 14 Hz
(median ⫾ width), while the higher-frequency FR group had a fre-
quency of 262 ⫾ 59 Hz. FR oscillations were significantly shorter in
duration compared with ripple oscillations (P ⬍ 0.0001). In regard to
the occurrence of FR and ripples in epileptic Hip and EC, the mean
ratio of the number of FR to ripples generated in areas ipsilateral to
seizure onset was significantly higher compared with the mean ratio of
FR to ripple generation from contralateral areas (P ⫽ 0.008). Further-
more, sites ipsilateral to seizure onset with hippocampal atrophy had
significantly higher ratios compared with sites contralateral to both
seizure onset and hippocampal atrophy (P ⫽ 0.001). These data
provide compelling quantitative and statistical evidence for the exis-
tence of two spectrally distinct groups of limbic oscillations that have
frequency and duration characteristics similar to those previously
described in epileptic rat and human Hip and EC. The strong associ-
ation between FR and regions of seizure initiation supports the view
that FR reflects pathological hypersynchronous events crucially asso-
ciated with seizure genesis.
INTRODUCTION
Increasing interest surrounds the investigation of fast oscil-
lations (⬎80 Hz) and their putative functional role in neural
processes. Studies have shown that oscillations within the
range of 100 to 200 Hz, termed “ripples,” are present in
non-primate hippocampus (Hip) and entorhinal cortex (EC)
(Buzsaki et al. 1992; Suzuki and Smith 1988). Ripple oscilla-
tions have also been recorded in neocortical areas of rodents
(Kandel and Buzsaki 1997) and cats (Grenier et al. 2001). The
discrete nature of these events, possessing durations between
25 and 75 ms (Chrobak and Buzsaki 1996), and the variation of
their occurrence across sleep/waking states have led some to
suggest that ripples may be involved in hippocampal and
neocortical wide-area networks associated with memory pro-
cessing (Buzsaki 1998; Chrobak and Buzsaki 1996; Grenier et
al. 2001; Siapas and Wilson 1998). In addition, somatosensory-
evoked oscillations (⬎200 Hz) have been recorded in both
rodent and human somatosensory cortex and presumably re-
flect the coordinated discharge of neurons involved with the
processing of incoming sensory information (Curio et al. 1994;
Jones and Barth 1999; Jones et al. 2000).
In contrast to the physiologically normal fast oscillatory
activity described in the preceding text, high-frequency activity
has been recorded preceding the onset of seizures in epileptic
patients (Fisher et al. 1992) and the oscillatory characteristics
of such activity described (Traub et al. 2001). Two recent
papers have identified the presence of high-frequency oscilla-
tions in Hip and EC areas of patients with temporal lobe
epilepsy (Bragin et al. 1999a,b). Results from these studies
showed that ripple oscillations were present bilaterally and
possessed many characteristics similar to those found in non-
primates, although they were of a lower frequency (80–160
Hz) than non-primate ripples. In addition to ripples, Bragin and
colleagues reported the occurrence of local field oscillations
that displayed higher spectral frequencies compared with rip-
ples and termed these oscillations “fast ripples” (FR; 250–500
Hz). This higher-frequency FR was limited to Hip and EC
areas ipsilateral to the area of seizure onset in humans; this was
consistent with the distribution of FR found only within sites
adjacent to the kindled or excitotoxic lesion in epileptic rodents
(Bragin et al. 1999a,b). These findings led to the proposal that
FR were pathological and reflected the hypersynchronous dis-
charge of locally interconnected principle neurons within epi-
Address for reprint requests: C. L. Wilson, 2155 Reed Neurological Re-
search Center, 710 Westwood Plaza, UCLA School of Medicine, Los Angeles,
CA 90095 (E-mail: clwilson@ucla.edu).
The costs of publication of this article were defrayed in part by the payment
of page charges. The article must therefore be hereby marked ‘‘advertisement’’
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
J Neurophysiol
88: 1743–1752, 2002; 10.1152/jn.00322.2002.
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