Neural masking by sub-threshold electric stimuli: animal and computer model results

Abstract

Electric stimuli can prosthetically excite auditory nerve fibers to partially restore sensory function to individuals impaired by profound or severe hearing loss. While basic response properties of electrically stimulated auditory nerve fibers (ANF) are known, responses to complex, time-changing stimuli used clinically are inadequately understood. We report that forward-masker pulse trains can enhance and reduce ANF responsiveness to subsequent stimuli and the novel observation that sub-threshold (nonspike-evoking) electric trains can reduce responsiveness to subsequent pulse-train stimuli. The effect is observed in the responses of cat ANFs and shown by a computational biophysical ANF model that simulates rate adaptation through integration of external potassium cation (K) channels. Both low-threshold (i.e., Klt) and high-threshold (Kht) channels were simulated at each node of Ranvier. Model versions without Klt channels did not produce the sub-threshold effect. These results suggest that some such accumulation mechanism, along with Klt channels, may underlie sub-threshold masking observed in cat ANF responses. As multichannel auditory prostheses typically present sub-threshold stimuli to various ANF subsets, there is clear relevance of these findings to clinical situations.

FIG. 1

Both the PSTHs from a cat ANF (left 2 columns) and the two K channel biophysical model (right 2 columns) exhibit sub-threshold masking of probe responses. In all cases, the masker was a 200-ms, 5,000-pulse/s train, and the probe was a 250-ms, 100-pulse/s train. Probe level is fixed, while masker level varies along each column. Masker levels are stated in milliamperes and decibels relative to the lowest masker level that evoked spikes. Shown near each masker PSTH is the mean overall spike rate. Masked probe responses are plotted in black; unmasked probe responses (the control condition) are in gray. Cat PSTHs for the probe stimuli show response reductions for both supra-threshold and sub-threshold maskers. At higher masker levels (A–C), probe response recovery was nonmonotonic, with larger first-pulse responses (asterisks). Sub-threshold masking is also seen in J and K of the computer model PSTHs. All ordinate axes have ranges from 0 to 1. The inset graphs in A and G show the details of the first 40 ms of each PSTH to better illustrate response probability alternations.

FIG. 2

The degree of forward masking of cat ANF responses to probe trains depends on masker level and masker pulse rate. Individual cat ANF recovery ratios are plotted in the graphs of the left column using small circles. Median values based on equal sample sizes are plotted using gray diamond symbols. The ratios are plotted versus effective masker level, with levels referenced to the lowest level that evoked spikes on a per-fiber basis. Probe responses are shown for 5,000 pulse/s maskers (upper graphs) and for 250 pulse/s maskers (lower graphs). Median values indicate that probe suppression is proportional to masker effective level and is greater for 5,000 pulse/s maskers. Feline medians are replotted in C and D, along with results from computer model variants: the “full model” that uses both Klt and Kht channels (circles) and the model lacking Klt channels (squares).

FIG. 3

The relationship between masker-evoked activity and probe-response masking differs across the two masking pulse rates used in this study. In A and B, individual ANF recovery ratios are plotted using open circles; gray diamonds indicate medians based on groups of 50 and 24 data subsets for 5,000 and 250 pulse/s masking, respectively. Linear regressions are shown using dashed lines. The histograms of C and D are based upon the sub-threshold data (i.e., 0 spike/s to the masker), with mean values indicated by the black diamonds.

FIG. 4

Plots of recovery ratios as functions of the response rate to the probe (abscissa) and the response rate to the masker (parameter). Data from individual ANFs are plotted along with median values (symbols connected by line segments). For low probe response rates, there are relatively high degrees of scatter and indications of error (i.e., ratios >1); this is likely due to error inherent to the use of ratios of small numbers and limited sample sizes. Note that only for limited masker and probe conditions can increases in probe level overcome forward-masking rate decrements.

FIG. 5

Biophysical model responses to pulse train stimuli, showing how membrane voltage (V_m) Kht and Klt ion currents (I_Kf and I_Ks, respectively) and extracelluar K concentration ([K_ext]) vary across stimulus presentation time. Currents through Klt channels result in accumulation of [K_ext], as does spike activity for the case of 5,000 pulse/s stimuli. Increase in [K_ext] is barely visible for the case of sub-threshold, 250 pulse/s stimuli. Dashed lines indicate the quiescent level of [K_ext]. The abscissae indicate time after the onset of each pulse train.

FIG. 6

Variations in the ratio of Klt and Kht channels influence the model’s predictions for rate adaptation (A, B), the recovery of ANFs to prior masking (C), and the ARP (D). A PSTH histograms from a selected cat ANF (upper left) and variations in the full model where different ρ_Klt/ρ_Kht ratios were explored. The cat PSTH was chosen as it was representative of ANF responses to 5,000 pulse/s trains that elicited a strong onset spike rate. The three model results in A all exhibit strong degrees of rate adaptation. Rate adaptation to 5,000 pulse/s trains for cat ANFs and model simulations are compared in B by plotting adaptation time constants for cat ANFs (small circles) and for four model variations that explored different ρ_Klt/ρ_Kht ratios. The mean and 1 standard deviation from the mean are plotted as horizontal lines (solid line: mean; dashed lines: ±1 standard deviation from the mean). In B, the cat ANF data were derived from Zhang et al. (2007). In C, the probe response recovery ratio (see text) for different model ρ_Klt/ρ_Kht ratios are compared with the mean value ±1 standard deviation of cat data obtained in the present study. Similar cat vs. model comparisons are provided for the ARP in D. In B–D, the same filled symbol types refer to the ρ_Klt/ρ_Kht ratios shown in B.