Multipulse Integration Research Articles

Electrically evoked compound action potential polarity sensitivity, refractory-recovery, and behavioral multi-pulse integration as potential indices of neural health in cochlear-implant recipients

Electrically evoked compound action potential polarity sensitivity, refractory-recovery, and behavioral multi-pulse integration as potential indices of neural health in cochlear-implant recipients

Assessing the Relationship Between Pitch Perception and Neural Health in Cochlear Implant Users.

Various neural health estimates have been shown to indicate the density of spiral ganglion neurons in animal and modeling studies of cochlear implants (CIs). However, when applied to human CI users, these neural health estimates based on psychophysical and electrophysiological measures are not consistently correlated with each other or with the speech recognition performance. This study investigated whether the neural health estimates have stronger correlations with the temporal and place pitch sensitivity than with the speech recognition performance. On five electrodes in 12 tested ears of eight adult CI users, polarity effect (PE), multipulse integration (MPI), and interphase gap (IPG) effect on the amplitude growth function (AGF) of electrically evoked compound action potential (ECAP) were measured to estimate neural health, while thresholds of amplitude modulation frequency ranking (AMFR) and virtual channel ranking (VCR) were measured to indicate temporal and place pitch sensitivity. AzBio sentence recognition in noise was measured using the clinical CI processor for each ear. The results showed significantly poorer AMFR and VCR thresholds on the basal electrodes than on the apical and middle electrodes. Across ears and electrodes, only the IPG offset effect on ECAP AGF had a nearly significant negative correlation with the VCR threshold after removing the outliers. No significant across-ear correlations were found between the mean neural health estimates, mean pitch-ranking thresholds, and AzBio sentence recognition score. This study suggests that the central axon demyelination reflected by the IPG offset effect may be important for the place pitch sensitivity of CI users and that the IPG offset effect may be used to predict the perceptual resolution of virtual channels for CI programming.

Evaluating and Comparing Behavioural and Electrophysiological Estimates of Neural Health in Cochlear Implant Users

Variations in neural health along the cochlea can degrade the spectral and temporal representation of sounds conveyed by cochlear implants (CIs). We evaluated and compared one electrophysiological measure and two behavioural measures that have been proposed as estimates of neural health patterns, in order to explore the extent to which the different measures provide converging and consistent neural health estimates. All measures were obtained from the same 11 users of the Cochlear Corporation CI. The two behavioural measures were multipulse integration (MPI) and the polarity effect (PE), both measured on each of seven electrodes per subject. MPI was measured as the difference between thresholds at 80 pps and 1000 pps, and PE as the difference in thresholds between cathodic- and anodic-centred quadraphasic (QP) 80-pps pulse trains. It has been proposed that good neural health corresponds to a large MPI and to a large negative PE (lower thresholds for cathodic than anodic pulses). The electrophysiological measure was the effect of interphase gap (IPG) on the offset of the ECAP amplitude growth function (AGF), which has been correlated with spiral ganglion neuron density in guinea pigs. This ‘IPG offset’ was obtained on the same subset of electrodes used for the behavioural measures. Despite high test–retest reliability, there were no significant correlations between the neural health estimates for either within-subject comparisons across the electrode array, or between-subject comparisons of the means. A phenomenological model of a population of spiral ganglion neurons was then used to investigate physiological mechanisms that might underlie the different neural health estimates. The combined experimental and modelling results provide evidence that PE, MPI and IPG offset may reflect different characteristics of the electrode-neural interface.

Effects of Electrode Location on Estimates of Neural Health in Humans with Cochlear Implants.

There are a number of psychophysical and electrophysiological measures that are correlated with SGN density in animal models, and these same measures can be performed in humans with cochlear implants (CIs). Thus, these measures are potentially applicable in humans for estimating the condition of the neural population (so called "neural health" or "cochlear health") at individual sites along the electrode array and possibly adjusting the stimulation strategy in the CI sound processor accordingly. Some measures used to estimate neural health in animals have included the electrically evoked compound potential (ECAP), psychophysical detection thresholds, and multipulse integration (MPI). With regard to ECAP measures, it has been shown that the change in the ECAP response as a function of increasing the stimulus interphase gap ("IPG Effect") also reflects neural density in implanted animals. These animal studies have typically been conducted using preparations in which the electrode was in a fixed position with respect to the neural population, whereas in human cochlear implant users, the position of individual electrodes varies widely within an electrode array and also across subjects. The current study evaluated the effects of electrode location in the implanted cochlea (specifically medial-lateral location) on various electrophysiological and psychophysical measures in eleven human subjects. The results demonstrated that some measures of interest, specifically ECAP thresholds, psychophysical detection thresholds, and ECAP amplitude-growth function (AGF) linear slope, were significantly related to the distances between the electrode and mid-modiolar axis (MMA). These same measures were less strongly related or not significantly related to the electrode to medial wall (MW) distance. In contrast, neither the IPG Effect for the ECAP AGF slope or threshold, nor the MPI slopes were significantly related to MMA or MW distance from the electrodes. These results suggest that "within-channel" estimates of neural health such as the IPG Effect and MPI slope might be more suitable for estimating nerve condition in humans for clinical application since they appear to be relatively independent of electrode position.

The time and place of cochlear implant pitch perception

It is well established that cochlear implant users can perceive pitch associated with pulse train stimulation rate, but that rate sensitivity diminishes above 300 pps. However, there have been multiple reported cases of individuals sensitive to stimulation rates well above 300 pps. Furthermore, Goldsworthy and Shannon (2014) demonstrated that sensitivity to stimulation rate could be improved through psychophysical training. The goal of the present study is to identify factors affecting rate sensitivity in cochlear implant users, including age, etiology, and duration of deafness, electrode location, stimulation mode, neural health as measured by multipulse integration, and spatial tuning as measured by forward masked thresholds. Adult cochlear implant users serve as subjects in a 3-week protocol that includes 4 hours per week of electrode psychophysics conducted in the laboratory and 30 minute daily auditory listening exercises conducted at home. Results indicate that cochlear implant users with minimal psychophysical training consistently discriminate rate differences at least as high as 800 pps. Emerging trends show a group effect with a monopolar stimulation mode and basal cochlear location benefit. We will report on the effect of the factors affecting rate sensitivity for this ongoing study.

Evaluating Multipulse Integration as a Neural-Health Correlate in Human Cochlear Implant Users: Effects of Stimulation Mode.

Previous psychophysical studies have shown that a steep detection-threshold-versus-stimulation-rate function (multipulse integration; MPI) is associated with laterally positioned electrodes producing a broad neural excitation pattern. These findings are consistent with steep MPI depending on either a certain width of neural excitation allowing a large population of neurons operating at a low point on their dynamic range to respond to an increase in stimulation rate or a certain slope of excitation pattern that allows recruitment of neurons at the excitation periphery. Results of the current study provide additional support for these mechanisms by demonstrating significantly flattened MPI functions in narrow bipolar than monopolar stimulation. The study further examined the relationship between the steepness of the psychometric functions for detection (d' versus log current level) and MPI. In contrast to findings in monopolar stimulation, current data measured in bipolar stimulation suggest that steepness of the psychometric functions explained a moderate amount of the across-site variance in MPI. Steepness of the psychometric functions, however, cannot explain why MPI flattened in bipolar stimulation, since slopes of the psychometric functions were comparable in the two stimulation modes. Lastly, our results show that across-site mean MPI measured in monopolar and bipolar stimulation correlated with speech recognition in opposite signs, with steeper monopolar MPI being associated with poorer performance but steeper bipolar MPI being associated with better performance. If steeper MPI requires broad stimulation of the cochlea, the correlation between monopolar MPI and speech recognition can be interpreted as the detrimental effect of poor spectral resolution on speech recognition. Assuming bipolar stimulation produces narrow excitation, and MPI measured in bipolar stimulation reflects primarily responses of the on-site neurons, the correlation between bipolar MPI and speech recognition can be understood in light of the importance of neural survival for speech recognition.

Dynamic programming based adaptive step integration method for maneuvering fluctuating target detection

An adaptive long time integration method based on dynamic programming (DP) is proposed for the detection of high speed maneuvering fluctuating targets. The proposed method is aimed at detecting a target with an unpredictable range migration and fluctuating echoes by jointly applying three main ideas: the improved DP procedure that could search the maneuver position and velocity at each frame; the multi-pulse integration that could suppress the influence of fluctuation; and the adaptive step with fading factor that could allow the integration time to be suitable for each searching velocity. Compared with the existing methods, the target energy could be integrated along its trajectory using the proposed method without estimating the specific motion parameters, which makes the proposed method applicable to a target with arbitrary motion. Simulation results and performance comparisons show the superiority of the proposed method.

Evaluating Multipulse Integration as a Neural-Health Correlate in Human Cochlear-Implant Users: Relationship to Psychometric Functions for Detection

In electrical hearing, multipulse integration (MPI) describes the rate at which detection threshold decreases with increasing stimulation rate in a fixed-duration pulse train. In human subjects, MPI has been shown to be dependent on the psychophysically estimated spread of neural excitation at a high stimulation rate, with broader spread predicting greater integration. The first aim of the present study was to replicate this finding using alternative methods for measuring MPI and spread of neural excitation. The second aim was to test the hypothesis that MPI is related to the slope of the psychometric function for detection. Specifically, a steep d’ versus stimulus level function would predict shallow MPI since the amount of current reduction necessary to compensate for an increase in stimulation rate to maintain threshold would be small. The MPI function was measured by obtaining adaptive detection thresholds at 160 and 640 pulses per second. Spread of neural excitation was measured by forward-masked psychophysical tuning curves. All psychophysical testing was performed in a monopolar stimulation mode (MP 1 + 2). Results showed that MPI was correlated with the slopes of the tuning curves, with broader tuning predicting steeper MPI, confirming the earlier finding. However, there was no relationship between MPI and the slopes of the psychometric functions. These results suggest that a broad stimulation of the cochlea facilitates MPI. MPI however is not related to the estimated neural excitation growth with current level near the behavioral threshold, at least in monopolar stimulation.

Evaluating multipulse integration as a neural-health correlate in human cochlear-implant users: Relationship to spatial selectivity.

The decrease of psychophysical detection thresholds as a function of pulse rate for a fixed-duration electrical pulse train is referred to as multipulse integration (MPI). The MPI slopes correlate with anatomical and physiological indices of cochlear health in guinea pigs with cochlear implants. The aim of the current study was to assess whether the MPI slopes were related to the spatial spread of activation by electrical stimulation. The hypothesis was that MPI is dependent on the total number of excitable neurons at the stimulation site, with broader neural excitation producing a steeper threshold decrease as a function of stimulation rate. MPI functions were measured at all stimulation sites in 22-site electrode arrays in human subjects. Some sites with steep MPI functions and other sites with shallow functions were assessed for spatial spread of excitation at 900 pps using a forward-masking paradigm. The results showed a correlation between the slopes of the forward-masking functions and the steepness of MPI, with broader stimulation predicting greater integration. The results are consistent with the idea that integration of multiple pulses in a pulse train relies on the number of excitable neurons at the stimulation site.

The trade-off relationship between spatial tuning and multipulse integration in human subjects with cochlear implants

Guinea pigs studies have shown a correlation between the slope of the function relating psychophysical detection thresholds to pulse rate (known as multipulse integration) and the spiral ganglion cell density in electrical stimulation. If this relationship holds true in human subjects with cochlear implants, we hypothesize that multipulse integration should reduce (i.e., become shallow sloped) at stimulation sites with sharp tuning or when electrode configuration changes from broad (monopolar) to focused stimulation (bipolar). Multipulse integration was measured at all stimulation sites using two pulse rates with phase duration of 75 us in a monopolar stimulation mode (MP1 + 2) and bipolar stimulation mode (BP + 0). At selected stimulation sites, a psychophysical spatial tuning curve was also measured using a forward-masking paradigm. The multipulse integration slopes were steeper with MP electrode configuration than with BP. In MP mode, the multipulse integration slopes were steeper at stimulation sites ...

Evaluating multipulse integration as a neural-health correlate in human cochlear-implant users: Relationship to forward-masking recovery.

The present study evaluated the slopes of threshold-versus-pulse-rate functions (multipulse integration, MPI) in humans with cochlear implants in relation to recovery from 300-ms forward maskers. MPI has been correlated with spiral ganglion cell density in animals. The present study showed that steeper MPI functions were correlated with faster recovery from forward masking. The findings suggested that the variations in the MPI slopes are explained not only by the quantity of neurons contributing to the integration process but also by the neurons' temporal response characteristics and possibly central inhibition.

Integration of Pulse Trains in Humans and Guinea Pigs with Cochlear Implants.

Temporal integration (TI; threshold versus stimulus duration) functions and multipulse integration (MPI; threshold versus pulse rate) functions were measured behaviorally in guinea pigs and humans with cochlear implants. Thresholds decreased with stimulus duration at a fixed pulse rate and with pulse rate at a fixed stimulus duration. The rates of threshold decrease (slopes) of the TI and MPI functions were not statistically different between the guinea pig and human subject groups. A characteristic of the integration functions that the two groups shared was that the slopes of the TI functions were similar in magnitude to slopes of the MPI function only at low pulse rates (< approximately 300 pulses per second). This is consistent with the notion that the TI functions and the MPI functions at the low rates are mediated by a mechanism of long-term integration described in the statistical "multiple looks" model. Histological analysis of the guinea pig cochleae suggested that the slopes of both the MPI and the TI functions were dependent on sensory and neural health near the stimulated regions. The strongest predictor for spiral ganglion cell densities measured near the stimulation sites was the slope of the MPI functions below 1,000 pps. Several mechanisms may be considered to account for the association of shallow integration functions with poor sensory and neural status. These mechanisms are related to abnormal across-fiber synchronization, increased refractoriness and adaptation with impaired neural function, and steep growth of neural excitation with current level associated with neural pathology. The slope of the integration functions can potentially be used as a non-invasive measure for identifying stimulation sites with poor neural health and selecting those sites for removal or rehabilitation, but these applications remain to be tested.

Relationship between multipulse integration and speech recognition with cochlear implants.

Comparisons of performance with cochlear implants and postmortem conditions in the cochlea in humans have shown mixed results. The limitations in those studies favor the use of within-subject designs and non-invasive measures to estimate cochlear conditions. One non-invasive correlate of cochlear health is multipulse integration, established in an animal model. The present study used this measure to relate neural health in human cochlear implant users to their speech recognition performance. The multipulse-integration slopes were derived based on psychophysical detection thresholds measured for two pulse rates (80 and 640 pulses per second). A within-subject design was used in eight subjects with bilateral implants where the direction and magnitude of ear differences in the multipulse-integration slopes were compared with those of the speech-recognition results. The speech measures included speech reception threshold for sentences and phoneme recognition in noise. The magnitude of ear difference in the integration slopes was significantly correlated with the magnitude of ear difference in speech reception thresholds, consonant recognition in noise, and transmission of place of articulation of consonants. These results suggest that multipulse integration predicts speech recognition in noise and perception of features that use dynamic spectral cues.

Characteristics of detection thresholds and maximum comfortable loudness levels as a function of pulse rate in human cochlear implant users

The ability of an implanted ear to integrate multiple pulses, as measured by the slopes of detection threshold level (T level) versus pulse rate functions, may reflect cochlear health in the cochlea, as suggested by previous animal studies (Kang et al., 2010; Pfingst et al., 2011). In the current study, we examined the slopes of T level versus pulse rate functions in human subjects with cochlear implants. Typically, T levels decrease as a function of pulse rate, consistent with a multipulse integration mechanism. The magnitudes of the slopes of the T level versus pulse rate functions obtained from the human subjects were comparable to those reported in the animal studies. The slopes varied across stimulation sites, but did not change systematically along the tonotopic axis. This suggests that the slopes are dependent on local conditions near the individual stimulation sites. The characteristics of these functions were also similar to those found in animals in that the slopes for higher pulse rates were steeper than those for the lower pulse rates, consistent with a combined effect of multipulse integration and cumulative partial depolarization mechanisms at rates above 1000 pps. The maximum comfortable loudness level (C level) versus pulse rate functions were also examined to determine the effect of level on the slopes. Slopes of C-level functions were shallower than those for the T-level functions and were not correlated with those of the T-level functions, so the mechanisms underlying these two functions are probably not identical. The slopes of the T- or C-level functions were not dependent on stimulus-current level. Based on these results, we suggest that slopes of T level versus pulse rate functions might be a useful measure for estimating nerve survival in the cochlea in regions close to the stimulation sites.

Detection of pulse trains in the electrically stimulated cochlea: effects of cochlear health.

Perception of electrical stimuli varies widely across users of cochlear implants and across stimulation sites in individual users. It is commonly assumed that the ability of subjects to detect and discriminate electrical signals is dependent, in part, on conditions in the implanted cochlea, but evidence supporting that hypothesis is sparse. The objective of this study was to define specific relationships between the survival of tissues near the implanted electrodes and the functional responses to electrical stimulation of those electrodes. Psychophysical and neurophysiological procedures were used to assess stimulus detection as a function of pulse rate under the various degrees of cochlear pathology. Cochlear morphology, assessed post-mortem, ranged from near-normal numbers of hair cells, peripheral processes and spiral ganglion cells, to complete absence of hair cells and peripheral processes and small numbers of surviving spiral ganglion cells. The psychophysical and neurophysiological studies indicated that slopes and levels of the threshold versus pulse rate functions reflected multipulse integration throughout the 200 ms pulse train with an additional contribution of interactions between adjacent pulses at high pulse rates. The amount of multipulse integration was correlated with the health of the implanted cochlea with implications for perception of more complex prosthetic stimuli.