Ultrafast oscillations in the human brain and their functional significance

The upper frequency limit of human brain activity remains unknown. Using ultrahigh sampling rate (≥20 kHz) intracranial microelectroencephalography, this study aimed to systematically explore and quantitatively characterize brain field oscillations beyond the established high-frequency oscillation range (>2 kHz), and to determine their relationship to epileptogenic tissue.

We analyzed intracranial electroencephalographic recordings from 15 patients with drug-resistant epilepsy, comprising 466 microcontacts and 434 macrocontacts implanted in mesiotemporal structures across four international epilepsy centers. A custom spectrogram-based detector optimized for ultrahigh frequencies was developed to identify ultrafast oscillations (UFOs; >2 kHz). UFO rates were assessed in epileptic (successfully resected) and nonepileptic hippocampi and compared with established electrophysiological biomarkers, including interictal epileptiform discharges, ripples, and fast ripples. Statistical comparisons were performed using mixed-effects models to account for intersubject and interelectrode variability.

We identified a previously undescribed class of short-duration oscillatory events spanning 2-8 kHz. UFOs occurred at significantly higher rates in epileptic compared with nonepileptic mesiotemporal regions, with the strongest differentiation observed in the 2-3-kHz band. Two distinct UFO phenotypes were consistently observed: (1) spindlelike, narrow-band oscillations and (2) sharp-onset, rapidly decaying bursts. Both forms were prevalent within epileptic hippocampi but were exceedingly rare in nonepileptic structures. UFOs exhibited pronounced temporal intermittency and spatial focality and frequently arose independently of ripples, fast ripples, and very high-frequency oscillations, indicating that they represent a distinct electrophysiological phenomenon. Macrocontacts detected UFOs only exceptionally, highlighting the necessity of microelectrode recordings to capture activity in this ultrahigh-frequency regime.

These findings substantially extend the known frequency range of human brain field activity and identify ultrafast oscillations as a novel biomarker of neuronal hyperexcitability. UFOs likely reflect pathological microcircuit dynamics inaccessible to conventional clinical recordings and provide new insights into the organization and pathophysiology of epileptogenic networks.