PMC

(Top panel) Interictal epileptiform spike microwire and adjacent clinical macroelectrodes (Pt #3). The after-coming slow-wave seen on the referential macroelectrode recording is not present on the microwire because of the local recording reference used for microwires. (Lower) Unfiltered and high-pass filtered (>80Hz) microwire recordings highlighting the high-frequency oscillation that is not present on adjacent macroelectrode recording. The high-pass filtered microwire recording (600–6000Hz) shows robust multi-unit activity in association with the fast-ripple oscillation.

Histograms(n =7 patients) show the total number of interictal HFO versus frequency recorded from clinical macroelectrodes (hatched) and microwires (open). The distribution of HFO events are qualitatively different for macroelectrode and microwires. The distribution of HFO recorded from the microwires demonstrates a broad continuum of events extending over the ripple and fast-ripple frequency range. In contrast, the distribution of HFO recorded from the clinical macroelectrodes decreases rapidly with frequency, and only rare fast-ripple HFO were recorded. The average ripple frequency (80–250Hz), HFO recorded from microwires was greater than HFO recorded from clinical macroelectrodes (143.3 ± 49.3 Hz versus 116.3 ± 38.4, P=0.0001).

Five seconds of raw iEEG (Pt#2) recorded from mesial temporal lobe using eight-contact hybrid depth electrode (). From the top, channels 1–7 (red) are from a microwire bundle extending from the electrode tip, channels 8–15 are the clinical macroelectrodes (blue) and the channels 16–23 are the shaft microwires. Channels with poor signal omitted from figure. Note fast-ripple oscillations on microwire #5 (underlined) that are not apparent on adjacent microwires or clinical macroelectrode (see also ). (Note: microwire channels with significant artifact not shown).

(A) MRI showing hybrid depth electrode (Adtech, Inc.) implanted along the longitudinal axis of the hippocampus via a posterior burr hole (Patient #1). The hybrid depth electrodes are composed of eight clinical macroelectrodes (blue), nine microwires (black) exiting the tip of the depth and nine radially oriented microwires along the shaft of the depth. The first clinical macrocontact is targeted at the amygdala. (B) Left temporal craniotomy (Patient #3) showing a 4× 6 subdural grid over temporal neocortex and hybrid depth electrodes placed through the grid into mesial temporal structures. The hybrid depth electrodes used for lateral approach are composed of 4 clinical macroelectrodes (blue), 9 microwires (black) exiting the tip of the depth and 18 microwires along the depth shaft. (C) Spectrum of human brain activity recorded from the hybrid depth electrodes.

(A) The total number of verified HFO (ripple and FR) for each patient (n =7) in the SOZ and non-SOZ. (B) Representative HFO examples. Each plot shows three views of HFO activity over a 300 ms epoch: (top) unfiltered EEG with an HFO event centred at 150ms, (middle) high-pass filtered EEG (80–1000Hz), (bottom) spectrogram (2.6 ms window). Note that HFOs are primarily characterized by a sharp spectral mode in the FR (a) or ripple frequency range (b). However, many HFOs exhibit more complicated time–frequency structure (c– e), with high-frequency onset followed by slowing of the frequency of the oscillatory event, or conversely ripple frequency at onset that evolved to higher frequency (f). The spectral complexity of these HFEO events highlights the difficulty assigning a single representative frequency.

Kurskal–Wallis analysis of variance (test statistic=32.34, P=3.5 × 10⁻⁵) was applied to three groups of variables: HFO frequency range (ripple/FR), electrode type (microwire/macroelectrode) and brain region of interest (seizure onset/non-seizure onset). Box-plots and the results from post hoc analysis using Wilcoxon rank sum (***P<0.002, **P<0.01, *P<0.05) are shown. The lower and upper borders of the box-plots, 25 and 75% percentile of the data, contain the data median indicated by the red line. The whiskers extend over the entire range of the data, and data outliers are indicated by a red cross. The number of microwire ripple (R_m) and fast ripple (FR_m) oscillations are increased in the SOZ compared to non-seizure onset regions (non-SOZ). The number of macroelectrode ripple (R_M) and fast ripple (FR_M) oscillations were increased in the SOZ compared to non-SOZ, but less significance for fast-ripple HFO. The microwire electrodes detect significantly more fast-ripple HFO compared to the clinical macroelectrodes.