SUMMARYPurpose: High-frequency oscillations (HFOs) known as ripples and fast ripples (250-500 Hz) can be recorded from macroelectrodes inserted in patients with intractable focal epilepsy. They are most likely linked to epileptogenesis and have been found in the seizure onset zone (SOZ) of human ictal and interictal recordings. HFOs occur frequently at the time of interictal spikes, but were also found independently. This study analyses the relationship between spikes and HFOs and the occurrence of HFOs in nonspiking channels. Methods: Intracerebral EEGs of 10 patients with intractable focal epilepsy were studied using macroelectrodes. Rates of HFOs within and outside spikes, the overlap between events, event durations, and the percentage of spikes carrying HFOs were calculated and compared according to anatomical localization, spiking activity, and relationship to the SOZ.Results: HFOs were found in all patients, significantly more within mesial temporal lobe structures than in neocortex. HFOs could be seen in spiking as well as nonspiking channels in all structures. Rates and durations of HFOs were significantly higher in the SOZ than outside. It was possible to establish a rate of HFOs to identify the SOZ with better sensitivity and specificity than with the rate of spikes. Discussion: HFOs occurred to a large extent independently of spikes. They are most frequent in mesial temporal structures. They are prominent in the SOZ and provide additional information on epileptogenicity independently of spikes. It was possible to identify the SOZ with a high specificity by looking at only 10 min of HFO activity.

Discrete high-frequency oscillations (HFOs) in the range of 100-500 Hz have previously been recorded in human epileptic brains using depth microelectrodes. We describe for the first time similar oscillations in a cohort of unselected focal epileptic patients implanted with EEG macroelectrodes. Spectral analysis and visual inspection techniques were used to study seizures from 10 consecutive patients undergoing pre-surgical evaluation for medically refractory focal epilepsy. Four of these patients had focal seizure onset in the mesial temporal lobe, and in all 12 of their seizures, well-localized, segmental, very high frequency band (VHF: 250-500 Hz) oscillations were visually identified near the time of seizure onset from contacts in this zone. Increased high-frequency band (HF: 100-200 Hz) activity compared with the background was distinguished both visually and with spectral analysis later in the seizures of 3/4 mesial temporal patients, involving contacts in the generator region and, in one patient, areas of contralateral peri-hippocampal propagation. Three patients with well-defined neocortical seizure-onset areas also demonstrated focal HF or VHF oscillations confined to the seizure-onset channels during their eight seizures. No discrete HF or VHF activity was present in the poorly localized seizures from the remaining three patients. These results show that discrete HFOs can be recorded from human focal epileptic brain using depth macroelectrodes, and that they occur mostly in regions of primary epileptogenesis and rarely in regions of secondary spread. Absent high-frequency activity seems to indicate poor localization, whereas the presence of focal HFOs near the time of seizure onset may signify proximity to the epileptogenic focus in mesial temporal lobe and neocortical seizures. We postulate that focal HFOs recorded with depth macroelectrodes reflect the partial synchronization of very local oscillations such as those previously studied using microelectrodes, and result from interconnected small neuronal ensembles. Our finding that localized HFOs occur in varying anatomical structures and pathological conditions perhaps indicates commonality to diverse epileptogenic aetiologies.

The theory on the glymphatic convection mechanism of cerebrospinal fluid holds that cardiac pulsations in part pump cerebrospinal fluid from the peri-arterial spaces through the extracellular tissue into the peri-venous spaces facilitated by aquaporin water channels. Since cardiac pulses cannot be the sole mechanism of glymphatic propulsion, we searched for additional cerebrospinal fluid pulsations in the human brain with ultra-fast magnetic resonance encephalography. We detected three types of physiological mechanisms affecting cerebral cerebrospinal fluid pulsations: cardiac, respiratory, and very low frequency pulsations. The cardiac pulsations induce a negative magnetic resonance encephalography signal change in peri-arterial regions that extends centrifugally and covers the brain in &1 Hz cycles. The respiratory &0.3 Hz pulsations are centripetal periodical pulses that occur dominantly in peri-venous areas. The third type of pulsation was very low frequency (VLF 0.001-0.023 Hz) and low frequency (LF 0.023-0.73 Hz) waves that both propagate with unique spatiotemporal patterns. Our findings using critically sampled magnetic resonance encephalography open a new view into cerebral fluid dynamics. Since glymphatic system failure may precede protein accumulations in diseases such as Alzheimer's dementia, this methodological advance offers a novel approach to image brain fluid dynamics that potentially can enable early detection and intervention in neurodegenerative diseases.

High frequency oscillations (HFOs) called ripples (80-250 Hz) and fast ripples (FR, 250-500 Hz) can be recorded from intracerebral EEG macroelectrodes in patients with intractable epilepsy. HFOs occur predominantly in the seizure onset zone (SOZ) but their relationship to the underlying pathology is unknown. It was the aim of this study to investigate whether HFOs are specific to the SOZ or result from pathologically changed tissue, whether or not it is epileptogenic. Patients with different lesion types, namely mesial temporal atrophy (MTA), focal cortical dysplasia (FCD) and nodular heterotopias (NH) were investigated. Intracranial EEG was recorded from depth macroelectrodes with a sampling rate of 2000 Hz. Ripples (80-250 Hz) and Fast Ripples (250-500 Hz) were visually marked in 12 patients: five with MTA, four with FCD and three with NH. Rates of events were statistically compared in channels in four areas: lesional SOZ, non-lesional SOZ, lesional non-SOZ and non-lesional non-SOZ. HFO rates were clearly more linked to the SOZ than to the lesion. They were highest in areas in which lesion and SOZ overlap, but in patients with a SOZ outside the lesion, such as in NHs, HFO rates were clearly higher in the non-lesional SOZ than in the inactive lesions. No specific HFO pattern could be identified for the different lesion types. The findings suggest that HFOs represent a marker for SOZ areas independent of the underlying pathology and that pathologic tissue changes alone do not lead to high rates of HFOs.