Using Interleaved Stimulation to Measure the Size and Selectivity of the Sustained Phase-Locked Neural Response to Cochlear Implant Stimulation

Abstract

We measured the sustained neural response to electrical stimulation by a cochlear implant (CI). To do so, we interleaved two stimuli with frequencies F1 and F2 Hz and recorded a neural distortion response (NDR) at F2-F1 Hz. We show that, because any one time point contains only the F1 or F2 stimulus, the instantaneous nonlinearities typical of electrical artefact should not produce distortion at this frequency. However, if the stimulus is smoothed, such as by charge integration at the nerve membrane, subsequent (neural) nonlinearities can produce a component at F2-F1 Hz. We stimulated a single CI electrode with interleaved sinusoids or interleaved amplitude-modulated pulse trains such that F2 = 1.5F1, and found no evidence for an NDR when F2-F1 was between 90 and 120 Hz. However, interleaved amplitude-modulated pulse trains with F2-F1~40 Hz revealed a substantial NDR with a group delay of about 45 ms, consistent with a thalamic and/or cortical response. The NDR could be measured even from recording electrodes adjacent to the implant and at the highest pulse rates (> 4000 pps) used clinically. We then measured the selectivity of this sustained response by presenting F1 and F2 to different electrodes and at different between-electrode distances. This revealed a broad tuning that, we argue, reflects the overlap between the excitation elicited by the two electrodes. Our results also provide a glimpse of the neural nonlinearity in the auditory system, unaffected by the biomechanical cochlear nonlinearities that accompany acoustic stimulation. Several potential clinical applications of our findings are discussed.

Keywords: cochlear implants; cortical response; electrophysiology; neural nonlinearity; psychophysics.

Fig. 1

A) Frequency spectrum of an analogue dyad consisting of two superimposed sinusoids F1 (80 Hz) and F2 (120 Hz). A 35-ms portion of the waveform is shown on the left. B) An instantaneous nonlinearity (such as could occur in the stimulating device), consisting of half-wave rectification and squaring, results in a DP with frequency F2-F1 = 40 Hz. This DP is also observed when the nonlinearity is preceded by smoothing, such as may occur in the auditory system (C). D) Stimulus produced by interleaving 200-μs sections of 80- and 120-Hz sinusoids. A zoomed-in section of the waveform is shown in the box on the far right. The nonlinearity now fails to produce a DP (part E, red oval) unless preceded by smoothing (F)

Fig. 2

Format is similar to Fig. 1. A) Amplitude-modulating a 4644-pps pulse train by the sum of two modulators (F1 + F2 Hz) produces a DP when the stimulus is passed through a nonlinearity (B). A somewhat larger DP arises when the nonlinearity is preceded by temporal smoothing (C). Interleaving two 2322-pps pulse trains that are separately modulated at F1 and F2 Hz (part D) does not produce a DP when the stimulus is passed through a nonlinearity (red oval, part E). Preceding the nonlinearity with temporal smoothing causes the DP to re-appear (part F)

Fig. 3

FFT of recordings from a fresh-frozen cadaver head in response to analogue dyads consisting of component frequencies of approximately F1 = 110 Hz and F2 = 220 Hz. Amplitudes of these primary frequencies are shown in each panel in blue and red text for F1 and F2, respectively. A distortion product at F2-F1 = 110 Hz is observed with an amplitude, indicated in orange text, that differs between (A) F1 and F2 superimposed, presented to the same electrode, B) F1 and F2 interleaved, presented to the same electrodes, and C) F1 and F2 interleaved and presented separately to adjacent electrodes

Fig. 4

FFT of recordings from three subjects implanted with the Advanced Bionics device in response to analogue dyads consisting of component frequencies of approximately F1 = 110 Hz and F2 = 220 Hz. Amplitudes of these primary frequencies are shown in each panel in blue and red text for F1 and F2, respectively. A distortion product at F2-F1 = 110 Hz is observed with an amplitude, indicated in orange text when F1 and F2 are interleaved on the same electrode (left panels) but not when presented separately to different electrodes (right panels). The amplitude of the component at F2-F1 Hz is shown only when significantly greater than the background noise

Fig. 5

FFT of recordings from two subjects implanted with a cochlear device in response to interleaved pulse trains. The difference frequency (F2-F1 Hz) is either 40 Hz (panels A, B), 90 Hz (C, D), or 120 Hz (E, F). The amplitude of the component at F2-F1 Hz is shown only when significantly greater than the background noise

Fig. 6

A) Phase vs frequency plots for the NDR (F2-F1 Hz, orange) and to an electrical artefact (F1 Hz, blue) in response to interleaved pulse trains having AM rates where F2-F1 is 37, 40, or 43 Hz. The abscissa shows F2-F1 Hz in orange and F1 Hz in blue. Solid lines show average data and faint lines show individual data. B) Box-and-whisker plots showing the group delay, derived from the functions shown in part A, for the NDR (orange) and F1-artefact (blue)

Fig. 7

Part A) shows the amplitude of the response at the NDR for the NDR (F2-F1 Hz, orange) and to an electrical artefact (F1 Hz, blue) in response to interleaved pulse trains having AM rates such that F2-F1 Hz is close to 40 Hz. Responses are shown for three electrodes illustrated schematically on the left. Electrode 2 was Iz. Electrodes 1 and 3 were P9 and P10 or vice versa, depending on which ear was implanted. Parts B, C, and D show phase vs frequency plots for recording electrodes 1, 2, and 3, respectively. Each of these three plots shows the NDR (F2-F1 Hz, orange) and to an electrical artefact (F1 Hz, blue) in response to interleaved pulse trains having AM rates where F2-F1 is 37, 40, or 43 Hz

Fig. 8

A) Average data and schematic of conditions in the spatial selectivity (“tuning”) experiment. The data plot shows the amplitude of the NDR as a function of the electrode that conveys the F2 stimulus. Red lines show the NDR amplitude when F1 is always presented to the most apical electrode tested (usually e20). Black lines show the NDR amplitude when F1 is presented to the same electrode as F2. Grey lines show the noise floor. B) Individual data

Fig. 9

Parts A–D show the amplitude and phase-frequency plots for the EASSR measured from three different recording electrodes, shown schematically on the top left. The format of these panels and the naming of electrodes is the same as for the NDR plots in Fig. 7. Part E) shows a scatterplot of EASSR vs NDR amplitudes for eight ears tested