Longevity and reliability of chronic unit recordings using the Utah, intracortical multi-electrode arrays

Abstract

Objective.Microelectrode arrays are standard tools for conducting chronic electrophysiological experiments, allowing researchers to simultaneously record from large numbers of neurons. Specifically, Utah electrode arrays (UEAs) have been utilized by scientists in many species, including rodents, rhesus macaques, marmosets, and human participants. The field of clinical human brain-computer interfaces currently relies on the UEA as a number of research groups have clearance from the United States Federal Drug Administration (FDA) for this device through the investigational device exemption pathway. Despite its widespread usage in systems neuroscience, few studies have comprehensively evaluated the reliability and signal quality of the Utah array over long periods of time in a large dataset.Approach.We collected and analyzed over 6000 recorded datasets from various cortical areas spanning almost nine years of experiments, totaling 17 rhesus macaques (Macaca mulatta) and 2 human subjects, and 55 separate microelectrode Utah arrays. The scale of this dataset allowed us to evaluate the average life of these arrays, based primarily on the signal-to-noise ratio of each electrode over time.Main results.Using implants in primary motor, premotor, prefrontal, and somatosensory cortices, we found that the average lifespan of available recordings from UEAs was 622 days, although we provide several examples of these UEAs lasting over 1000 days and one up to 9 years; human implants were also shown to last longer than non-human primate implants. We also found that electrode length did not affect longevity and quality, but iridium oxide metallization on the electrode tip exhibited superior yield as compared to platinum metallization.Significance.Understanding longevity and reliability of microelectrode array recordings allows researchers to set expectations and plan experiments accordingly and maximize the amount of high-quality data gathered. Our results suggest that one can expect chronic unit recordings to last at least two years, with the possibility for arrays to last the better part of a decade.

Trial registration: ClinicalTrials.gov NCT01364480 NCT01894802.

Keywords: chronic signal quality; cortex; electrode array reliability; human electrophysiology; longevity; non-human primate electrophysiology.

Conflict of interest statement

Conflicts of Interest

N.G.H. serves as a consultant for Blackrock Microsystems, Inc., the company that sells the multi-electrode arrays and acquisition system used in this study.

Creative Commons Attribution license.

Figures

Figure 1.

Example waveforms and signal-to-noise ratio (SNR) from a UEA recording session (Subject Mk, array MkM1c). SNR values are presented in the top left corner of each panel. Red SNR values indicate electrodes which exceeded the requisite SNR threshold of 1.5 to be considered as “good” electrodes included in subsequent analyses of array yield. The red line in each panel indicates the threshold across which a waveform must cross to be considered an action potential. Empty panels indicate electrodes in which less than fourteen spikes were detected within the given recording session, and therefore were not included in analysis.

Figure 2.

Summary heat map of signal-to-noise ratio (circle color) and array yield (circle size) over time for all array implants analyzed. Each colored circle denotes a single recording session. The color of the circle denotes the average SNR of the array for that given recording session. The size of the circle denotes the percentage of electrodes in that array that demonstrated a signal-to-noise ratio above a threshold of 1.5.

Figure 3.

Proportion of arrays exceeding a certain yield at month-to-month intervals post-implantation. Each line delineates a different percentage yield threshold. If an array is not recorded from in a given time window, it is not counted in the “proportion” estimate. After their last available recording date, arrays are counted in the proportion measurement, to accurately depict the degradation of arrays on average. However, arrays which ceased recording due to medical, hardware failure, or study end reasons (see Table 1) were not included in the proportion measurement after their last available recording date.

Figure 4.. Extended long-term performance for a subset of arrays.

a. Yield for long-term array implants as a function of days post-implantation. Lines indicate best fit linear regressions to the data for each array. All linear regressions are statistically significant (p < .05), save for “BoPMdb”, the only array whose regression displayed an upward trend. The recording quality metrics exhibit a discontinuity at day 565 for subject P1, due to a change in the spike threshold from −5.25 to −4.5 RMS, indicated by the vertical dashed lines. b. Example spike waveforms from one array implant (MkM1c) at regular intervals over nearly 9 years. SNR values are presented at the top left corner of each panel (red font denotes electrodes that exceeded an SNR threshold of 1.5). c. SNR of Monkey Mk’s recordings, over the lifetime of the implant.

Figure 5.

Reliability of viable chronic recordings over time. Shaded regions denote standard error of the mean. a. Average yield (blue) and SNR (red) over arrays with viable recordings (i.e. array recordings that were not terminated) versus number of days post-implantation for NHP implants. Full time range not shown (maximum lifetime is in excess of 3000 days). b. Close-up of average yield and SNR over the first 40 days post-implantation. A significant difference was observed between the first week and fourth week of recordings (p = 0.0122, 2-sample t-test, 2-tailed). c,d. equivalent statistics for human implants. Further details can be found in Downey et al., 2018 (8). The purple vertical line indicates the date at which the R.M.S. spike threshold was set to a different value during data collection (see methods for details). The change in the figure is due to a larger number of recordings becoming possible to average across, reducing variance in the estimate of yield and SNR. The green line indicates the date data collection with P1 ended.

Figure 6.. Effects of electrode tip metallization and electrode length on array performance in NHP implants.

a, c. The average yield for each six-month date window was calculated for each array; an average was then taken across all arrays with the same metallization or electrode length (short-1.0 mm, long-1.5 mm), respectively. Shaded regions for all plots indicate the standard error of the mean, across arrays. b, d. Average SNR based on metallization and electrode length, respectively. Statistical tests were corrected for multiple comparisons using Bonferroni correction. Stars indicate statistically significant differences between groups, Bonferroni corrected. Averages were calculated over recordings and arrays for which data was available for each time window. Only NHP data were used for this figure.

Figure 7.. Maximum possible yield.

a. Distribution of the maximum recorded electrode yield over all arrays, from 0% to 100% of possible electrodes. b. Distribution of dates when the maximum number of recorded channels occurred. Most maximum recording days occurred within the first 150 days post-implantation. This data rejects a chi-squared test of uniformity at a p-value of (p = .002)