Representation of amplitude modulation in the auditory cortex of the cat. I. The anterior auditory field (AAF)

The ability of cortical neurons to follow amplitude modulation (AM) of tones was examined in the anterior auditory cortical field (AAF) of anesthetized cats using multiple-unit recording techniques. Sinusoidal and rectangular modulations (100%) of a monaural carrier tone at the characteristic frequency of each location were presented to study the degree of response synchronization and changes in firing rate as a function of the modulation frequency. All investigated locations were tuned to a 'best modulation frequency' (BMF) as determined by synchronization measures. Almost all locations (94%) were tuned to a BMF as determined by spike rate. Maximal binaural-interaction strength was observed for modulation frequencies close to the BMF of neurons. For sinusoidal AM, a correlation (r = 0.63, P less than 0.01) between BMF and CF of neurons in AAF could be demonstrated for the synchronization of the response.     

Temporal modulation transfer functions for single neurons in the auditory midbrain of the leopard frog. Intensity and carrier-frequency dependence

The sensitivity for amplitude modulation was investigated for 77 neurons from the auditory midbrain of the leopard frog. The results show that tuning to modulation frequencies occurs in about one-third of the units but is quite varied in its appearance. Two slightly differing characterizations for this tuning have been used; the overall response or rate-Modulation Transfer Function and the synchronized response or temporal-MTF (tMTF). The relation between the two characterizations is given by the vector-strength. Only one-third of the units showed a vector-strength that was significantly different from zero. Another synchronization measure, the synchronization factor which is based on the auto-coincidence function, was significantly different from zero in about 3/4 of the units. The Best Modulation Frequency (BMF) and tuning band-width were found to be independent of both stimulus intensity and carrier frequency, although the average BMF for band-pass units was slightly higher for the amphibian papilla range of carrier frequencies than for the basilar papilla range (66 Hz vs. 49 Hz). The most frequent BMF for band-pass units was around 55 Hz, this does not correspond with the dominant modulation frequency of the mating call which is around 20 Hz. The synchronization measures were negatively correlated with intensity and independent of carrier frequency. The phase response of the tMTF was used to calculate the group delay. In contrast to the latency of the units the group delay was independent of stimulus intensity.     

The phase response of primary auditory afferents in a songbird (Sturnus vulgaris L.)

The effects of stimulus frequency and intensity on phase-locking characteristics of cochlear ganglion cells were studied in the starling. All cells showed phase-locking to tone stimuli within their response area. Phase-locking at CF is found on average 9 dB below discharge rate threshold. Phase-locking is best at 0.4 kHz and deteriorates with increasing frequency almost independently of CF. No phase-locking was evident for test frequencies above 3-4 kHz. Phase-locking in cells with CFs above 1.0 kHz is better below CF than at CF. For constant sound pressure, an increase in stimulus frequency always produced an increase in phase lag of the neural response. The phase vs. frequency data obtained at constant sound pressure can be reasonably approximated by straight line functions. The slopes of these functions indicate the latency of the neural response, and are correlated with the CFs of the respective cells; the latency tends to be longer in low-CF cells and shorter in high-CF cells. The latency decreases by 0.04 ms per 1 dB sound pressure increase. The response phase at CF is nearly stimulus level-independent. Increasing stimulus intensity causes increasing phase lag below CF and decreasing phase lag above CF. These results are compared to findings in other vertebrates and demonstrate the similarities of phase-locking characteristics despite the substantial anatomical differences among the vertebrate groups.     

Long-Term Frequency Tuning of Local Field Potentials in the Auditory Cortex of the Waking Guinea Pig

The goal of our study was to determine the extent of changes in frequency tuning in the auditory cortex over weeks. The subjects were awake adult male guinea pigs (n = 8) bearing electrodes chronically implanted in layers IV-VI of primary auditory cortex. Tuning was determined by presenting sequences of pure tone bursts (approximately 0.97-41.97 kHz, -20 to 80 dB, 100-ms tone duration, 5-ms rise-fall, 800-ms intertone intervals, 1.5-s intersequence interval) either in 0.5-octave steps (n = 5, 14 probes) or 0.25-octave steps (n = 3, 9 probes) delivered to the ear contralateral to recording sites. Tuning curves were determined for local field potentials (LFPs), which were tuned to frequency (negative potential, latency to peak 15-20 ms), repeatedly for up to 27 days (0.5 octave) or 12 days (0.25 octave). Characteristic frequency (CF), best frequency at 10 and 30 dB above absolute threshold (BF10, BF30), threshold (TH), and bandwidth (10 dB above threshold; BW) were measured. Absolute amplitude often decreased across weeks, necessitating normalization of amplitude. However, there were no significant trends in tuning over days for CF, BF10, or BF30 for either the half- or the quarter-octave group. Both groups exhibited random daily variations in frequency tuning, the quarter-octave group revealing larger variations averaging 0.228, 0.211, and 0.250 octave for CF, BF10, and BF30, respectively. Therefore, frequency tuning in waking animals does not exhibit directional drift over very long periods of time. However, daily tuning variations on the order of 0.20-0.25 octave indicate that the peaks of tuning curves (CF, BF) represent a preferred frequency range rather than a fixed frequency.     

Single-fibre and whole-nerve responses to clicks as a function of sound intensity in the guinea pig.

This paper describes a study of the intensity dependence of click-evoked responses of auditory-nerve fibres in relation to the simultaneously recorded compound action potential (CAP). Condensation and rarefaction clicks were presented to normal hearing guinea pigs over an intensity range of 60 dB. The recorded poststimulus time histograms (PSTHs) were characterized by the latency (tp), amplitude (Ap) and synchronization (Sp) of their dominant peak, parameters that are particularly important for the understanding of the CAP. For all fibres tp decreased monotonically with increasing intensity, in a continuous way for fibres with high characteristic frequency (CF greater than 3 kHz), and in discrete steps of one CF-cycle for low-CF (CF less than or equal to 3 kHz) fibres. An additional analysis of PSTH envelopes revealed that average latency shifts with intensity are similar for all CFs above 2 kHz. For all fibres Ap increased monotonically with intensity; the increase was stronger and maximum values were larger for low-CF than for high-CF fibres. A schematic model PSTH was then formulated on the basis of the experimental data. A sum of these model PSTHs from a hypothesized fibre population was convolved with an elemental unit response (Versnel et al., 1992) in order to simulate the compound action potential. Synthesized CAPs agreed with experimental CAPs in their main aspects.     

Temporal and spatial coding of periodicity information in the inferior colliculus of awake chinchilla (Chinchilla laniger)

Amplitude modulation responses and onset latencies of multi-unit recordings and evoked potentials were investigated in the central nucleus of inferior colliculus (ICC) in the awake chinchilla. Nine hundred and one recording sites with best frequencies between 60 and 30 kHz showed either phasic (18%), tonic (25%), or phasic-tonic (57%) responses. Of 554 sites tested for responses to modulation frequencies 73% were responsive and 57% showed clear preference for a narrow range of modulation frequencies. Well defined bandpass characteristics were found for 32% of rate modulation transfer functions (rate-MTFs) and 36% of synchronization MTFs (sync-MTFs). The highest best modulation frequency (BMF) of a bandpass rate-MTF was 600 Hz. Neurons with phasic responses to best-frequency tones showed strong phase coupling to modulation frequencies and were dominated by bandpass rate-MTFs and sync-MTFs. Most neurons with tonic responses showed bandpass tuning only for sync-MTFs. Both BMFs and onset latencies changed systematically across frequency-band laminae of the ICC. Low BMFs and long latencies were located medially and high BMFs and short latencies laterally. Latency distributions obtained with evoked potentials to clicks showed a similar gradient to the multi-unit data. These findings are in line with previous findings in different animals including humans and support the hypothesis that temporal processing results in a topographic arrangement orthogonal to the spectral processing axis, thus forming a second neural axis of the auditory system.     

Responses to Combinations of Tones in the Nuclei of the Lateral Lemniscus

Combination-sensitive neurons integrate specific spectral and temporal elements in biologically important sounds, and they may underlie the analysis of biosonar and social vocalizations. Combination-sensitive neurons are found in the forebrain of a variety of vertebrates. In the mustached bat, they also occur in the central nucleus of the inferior colliculus (ICC). However, it is not known where combination-sensitive response properties emerge. To address this question, we used a two-tone paradigm to examine responses of single units to combination stimuli in a brainstem structure, the nuclei of the lateral lemniscus (NLL). We recorded and histologically localized 101 single units in the NLL. The majority (82%) of units had a single excitatory frequency tuning curve. Seven units had two separate excitatory frequency tuning curves but displayed no combinatorial interaction. Twelve units were combination-sensitive. Of these, three units were facilitated by the combination of two separate frequency bands and nine units were inhibited by combinatorial stimuli. The three facilitatory neurons had excitatory responses tuned to the second harmonic constant frequency (CF2, 57-60 kHz) component of the biosonar signal and were facilitated by a second signal within the first harmonic (Hl, 24-30 kHz) of the biosonar call. Most of the inhibitory interactions occurred between signals in the frequency bands associated with the frequency-modulated (FM) components of the biosonar call. The strongest combinatorial effects (facilitatory and inhibitory) were elicited by simultaneous onset of the two signals (i.e., 0 ms delay). All combination-sensitive units were in the intermediate nucleus of the NLL (INLL), which in bats is a hypertrophied structure that projects strongly to combination-sensitive neurons in the ICC. Thus, the combination-sensitive neurons in the INLL may impart their response properties onto ICC neurons. However, the small number of facilitatory combination-sensitive neurons in the NLL suggests that the majority of these combinatorial responses originate in the ICC.     

Neural encoding of amplitude modulation within the auditory midbrain of squirrel monkeys

The neuronal responses to amplitude modulated (AM) sounds were investigated in the auditory midbrain of the squirrel monkey. Sinusoidally modulated tones and noise served as acoustic stimuli. In order to describe the response properties of collicular neurons, Fast-Fourier-Transformation (FFT), a cross-correlation algorithm and spike-rate counts were applied to translate the neuronal reactions into modulation transfer functions. FFT and cross-correlation defined a measure for synchronic- ity of the neuronal discharges with the modulation cycles. All neurons (542) responded selectively to AM-sounds insofar as all displayed a best modulation frequency (BMF). Most of them furthermore had a band-pass-like modulation transfer function, whose center frequencies were mainly between 8 and 128 Hz. Transfer functions obtained by spike-rate showed less selectivity: a relatively great number of neurons did not change their spike rate as a function of modulation frequency.

The results show that encoding of amplitude-modulated sounds occurs to a greater extent via phase locking of discharges than via changes in spike number. In the same way, changing modulation depth is processed: whereas spike rate on average remains constant between 100% and 0% modulation, there is a drastic reduction in synchronicity. No clear relationship was found between a unit's characteristic frequency and BMF; the same applied to BMF and recording place. The results furthermore show that amplitude modulations are encoded selectively in a band pass function in a non-human primate. The midbrain thereby occupies an intermediate position within the pathway from the periphery to the cortex. This form of temporal resolution probably underlies mechanisms caused by the increasing synaptic activity in the course of the pathway. This may indicate adaptation since those modulation frequencies embedded in this species' vocal repertoire fit quite well with the system's tuning properties for amplitude modulation.     

听神经病患者失匹配负波特征与言语识别率的关系

目的观察听神经病(auditory neuropathy,AN)患者失匹配负波(mismatch negativity,MMN)的基本特征及其与最大言语识别率(phonetic balanced maximum,PBmax)的关系。方法用IHS3099(Version3.82)型诱发电位仪对14例(19耳)AN患者和24例(24耳)听力正常者行MMN测试,用GSI-61双通道诊断型听力计和SONY Tc-Fx25盒式双声道立体声录音机及自行录制的单音节音素平衡词表磁带分别测试14例(19耳)AN患者和19例(19耳)听力正常者的PBmax,比较两组MMN潜伏期和振幅差异有无显著性意义,并分析MMN潜伏期和振幅与PBmax的相关性。结果与对照组相比,AN组MMN(强度差异和频率差异)潜伏期显著延长(P<0.01),AN组强度差异MMN振幅与对照组相比有显著性差异(P=0.019),两组频率差异MMN振幅无显著性差异(P=0.128);AN组频率差异和强度差异MMN潜伏期与PBmax呈部分负相关(r=-0.647,P<0.01;r=-0.708,P<0.01),对照组强度差异MMN潜伏期与PBmax也呈部分负相关(r=-0.643,P<0.05),但对照组频率差异MMN潜伏期与PBmax无相关性(r=-0.027,P=0.913)。结论MMN潜伏期相对稳定,振幅变异较大。AN组MMN潜伏期明显比对照组延长,在群体水平与PBmax呈部分负相关。MMN潜伏期在预估AN患者的言语识别能力方面有一定的意义。     

Compound action potentials and single unit responses to a 1 kHz haversine in the cat

The single-cycle 1 kHz haversine (one cycle of a 1 kHz sine wave beginning at -90 degrees) is a low-frequency impulsive stimulus which has been little use, but which has significant potential applications both as a clinical and a research tool. The auditory nerve compound action potential (CAP) and single unit discharge patterns evoked by a single-cycle 1 kHz haversine stimulus were studied in anesthetized cats. The haversine CAP waveform consisted of two or three short latency peaks with peak to peak intervals of about 1.0 ms. Latencies of the CAP peaks decreased with increased stimulus intensity and were also strongly dependent on stimulus polarity. Typically, CAP peak latencies changed by about 0.5 ms with stimulus polarity reversal. Single unit responses were classified by the peak latency pattern of their haversine post-stimulus time histograms (PSTHs). Low CF units had low thresholds and PSTHs resembling their click responses. High CF units had high thresholds and PSTHs comprised of one or two short latency peaks whose latencies were polarity-sensitive. Some units in an intermediate CF range (approximately 1.5-3.0 kHz) had PSTHs which were a transitional form between the high and low CF types of response. The unit discharge patterns strongly suggested a low frequency origin for the haversine CAP at all intensities.     

Comparison between local field potentials and unit cluster activity in primary auditory cortex and anterior auditory field in the cat

Multi-unit (MU) activity and local field potentials (LFP) were simultaneously recorded from 161 sites in the middle cortical layers of the primary auditory cortex (AI) and the anterior auditory field (AAF) in 51 cats. Responses were obtained for frequencies between 625 Hz and 40 kHz, at intensities from 75 dB SPL to threshold. We compared the response properties of MU activity and LFP triggers, in terms of characteristic frequency (CF), threshold at CF, minimum latency and frequency tuning-curve bandwidth 20 dB above threshold. On average, thresholds at CF were significantly lower for LFP events than those for MU spikes (4.6 dB for AI, and 3 dB for AAF). Minimum latencies were significantly shorter for LFP events than for MU spikes (1.5 ms in AI, and 1.7 ms in AAF). Frequency tuning curves were significantly broader for LFP events than those for MU spikes (1.0 octave in AI, and 1.3 octaves in AAF). In contrast, the CF was not significantly different between LFP events and MU spikes. The LFP results indicate that cortical neurons receive convergent sub-cortical inputs from a broad frequency range. The sharper tuning curves for MU activity compared to those of LFP events are likely the result of intracortical inhibitory processes.     

Changes in cat primary auditory cortex after minor-to-moderate pure-tone induced hearing loss

In this paper we present findings in the primary auditory cortex of cats exposed for 2 h to a 115 dB SPL, 6 kHz tone at 36 days, 56 days or 118 days after birth. We evaluate the effects of age at exposure, amount of hearing loss, and time after induction of trauma on the functional reorganization of the cortical tonotopic map. We found a fairly sharp demarcation in the amount of hearing loss (20-25 dB) that caused cortical reorganization. For localized hearing losses, unmasking of excitatory contributions of neighboring frequency regions was found. For cats showing reorganization of the tonotopic map, the frequency-tuning curve bandwidth at 20 dB above threshold at CF (BW(20dB)) increased with increasing threshold at CF. Threshold at CF, and BW(20dB) increased with time after exposure. Minimum spike latency was initially increased, but subsequently decreased with time after exposure at a rate that was two times faster in cats with reorganized cortex than in cats with normal tonotopic maps, to reach the same asymptotic value. Thresholds at CF were correlated with the peripheral hearing loss at near CF frequencies as estimated from ABR measurements. The correlation between BW(20dB) and CF threshold suggests that part of the reorganization could be due to 'residual' sensitivity of the high frequency neurons to not-affected lower or higher frequencies. However, for CFs above 6 kHz, the BW(20dB) for cats with reorganization of the tonotopic map was significantly lower (on average 0.3 octave, P<0.05) than for cats with normal tonotopic maps. This is not what one would expect in cases of pseudo-plasticity characterized by concurrent shifts in BW(20dB) and CF as a result of residual sensitivity to lower frequencies.     

Round-window recorded potential of single-fibre discharge (unit response) in normal and noise-damaged cochleas.

Unit responses (URs) of eighth-nerve fibres have been determined at the round window by spike-triggered averaging in both normal and pathological guinea pig cochleas. The pathology was mainly noise-induced damage. The URs have been analysed with respect to their dependence on the fibre's threshold, characteristic frequency (CF) and spontaneous rate (SR). The results from normal cochleas confirmed earlier data (Prijs, 1986): the UR has a diphasic waveform and the amplitude of its negative first peak is about 0.1 microV. From the six parameters (amplitude, latency, and width of the two peaks) by which the UR was described only the amplitude of the positive peak showed a significant variation with CF: a small decrease with increasing CF (CF-range 0.1 to 20 kHz). This finding may possibly be caused by oscillations in the spike-triggered average for low CFs. URs for most low- and medium-SR fibres were found to be large (greater than 0.3 microV). However, this result is interpreted as an artefact caused by synchrony of fibre spontaneous activity. In damaged cochleas only slight changes of the UR were found: the waveform duration became significantly shorter and on some occasions the positive peak increased in amplitude, but latency and amplitude of the negative component of the UR remained unchanged.     

Sensitivity of neurons in cat primary auditory cortex to tones and frequency-modulated stimuli. I: Effects of variation of stimulus parameters.

In the primary auditory cortex (AI) of barbiturate-anesthetized cats multi-unit responses to tones and to frequency-modulated (FM) tonal stimuli were analyzed. Characteristic frequency (CF), sharpness of tuning, minimum threshold, and dynamic range of spike count--intensity functions were determined. Minimum threshold and dynamic range were positively correlated. The response functions to unidirectional FM sweeps of varying linear rate of change of frequency (RCF) that traversed the excitatory frequency response areas (FRAs) displayed a variety of shapes. Preferences for fast RCFs (> 1000 kHz/s) were most common. Best RCF was not correlated with measures of sharpness of tuning. Directional preference and sensitivity were quantified by a DS index which varied with RCF. About two-thirds of the multi-unit responses showed a preference for downward sweeps. Directional sensitivity was independent of CF and independent of best RCF. Measurements of latencies of phasic responses to unidirectional FM sweeps of different RCF demonstrated that the discharges of a given multi-unit over its effective RCF range were initiated at the same instantaneous frequency (effective Fi), independent of RCF. Effective Fis fell within the excitatory FRA of a given multi-unit. The relationships of effective Fis to CF show that responses were evoked only when the frequency of the signal was modulated towards CF and not when modulated away from it, and that responses were initiated before the modulation reached CF. Changes in the range and depth of modulation had only minor, if any, effects on RCF response characteristics, FM directional sensitivity, and effective Fis, as long as the beginning and ending frequencies of FM sweeps fell outside a multi-unit's FRA. Stimulus intensity also had only moderate effects on RCF response characteristics and DS. However, effective Fis were influenced in systematic fashions; with increases in intensity, effective Fis to upward and downward sweeps decreased and increased, respectively. Thus, for higher intensities FM responses were initiated at instantaneous frequencies occurring earlier in the signal. The results are compared with previous data on tone and FM sensitivity of auditory neurons in cortical and subcortical structures, and mechanisms of FM rate and directional sensitivity are discussed. The topographic representations of these neuronal properties in AI are reported in the companion report.     

Forward masking of the auditory nerve neurophonic (ANN) and the frequency following response (FFR)

The forward masking behavior of two averaged neurophonic responses was examined in cats. The auditory nerve neurophonic (ANN) was recorded with bipolar electrodes placed on the auditory nerve as it exits the internal meatus. The frequency following response (FFR) was recorded using scalp electrodes placed at the vertex and below the stimulated ear. Masking functions (response amplitude vs masker level) for frequencies both above and below the probe frequency were recorded. From these masking functions, 30% iso-depression contours (forward masking tuning curves, FMTCs) were constructed. The time course of the recovery from forward masking was also examined. It was found that the forward masking behavior of these neurophonics have many similarities to the behavior of other responses recorded using psychophysical and physiological methods. However, forward masking of the ANN and FFR has a number of unusual features. First, the best masking frequency (BMF), which in most forward masking studies is equal to the probe frequency, can be off-set from the probe frequency by as much as an octave. Second, the masker level at BMF can be as much as 30 dB below the probe level. Third, the magnitude of both of these off-sets is a function of the probe level. Fourth, low level neurophonic response could be enhanced by some forward 'maskers'. The features of neurophonic forward masking are discussed and a model of the neurophonics is suggested. This model is based on the spatial distribution of phase and amplitude in the phase-locked activity in the auditory nerve and it can qualitatively account for many of the properties of the neurophonics.     

Effects of interaural time differences on the responses of chinchilla inferior colliculus neurons to consonant-vowel syllables

The responses of 100 inferior colliculus neurons to syllables differing in voice onset time (VOT) presented binaurally were studied. As in a previous study of monaural responses (Chen et al., 1996), the responses consisted of 1-3 response 'components', referred to as release responses, VOT responses or vowel responses. The discharge rate of all response components could vary cyclically with the interaural time difference (ITD). The maximal rate often occurred at an ITD around +0.2 ms (contralateral ear leading). Response frequencies (RF) based on the periodicity of the delay curves varied with the characteristic frequency (CF) and VOT. RF also varied across response components. Overall, RF was correlated with the 'most effective frequency', the spectral component with the highest amplitude, relative to the tuning curve. VOT response latency for a given syllable could change by a few ms with ITD, but those changes were small, relative to the range of latencies observed over the entire range of VOTs. Changes in ITD produced large changes in the overall shape of the peristimulus time histogram. There was no relation between the histogram shape and perceptual consonant categories.     

Delay analysis in the auditory brainstem of the rat: comparison with click latency

Many cells in the auditory brainstem 'phase lock' to tone stimuli. From the changing phase relationship between the stimulus and the neural response in phase-locking cells, the delay between them can be estimated. This delay, however, is consistently greater than the latency measured in response to click stimuli, an important discrepancy. In this paper the different measures of delay, namely phase delay, group delay and signal-front delay are re-examined. An improved method for computing the average group delay is presented, which accounts for the cyclical nature of the phase data. Data were collected from units in successive processing sites of auditory pathway: the auditory nerve, the cochlear nucleus, the trapezoid body and the medial nucleus of the trapezoid body. Low-characteristic frequency (CF) units gave multimodal post-stimulus-time histograms in response to clicks, and showed stepwise decreases in latency with increasing intensity, with the appearance of earlier peaks in the response, rather than shifts in the timing of the peaks. The separation of peaks corresponded to the inverse of the unit's CF. High-CF units also showed a decline in click latency with intensity, but to a lesser degree than low CF units. We present an analysis which explains the difference between click latency and delay, and which in contrast to previous accounts is experimentally testable. We demonstrate that this new framework accounts for the discrepancy between the two measures of delay, and in addition accounts for the observed stepwise shifts in click latency for low-CF units.     

Electrophysiological Validation of a Human Prototype Auditory Midbrain Implant in a Guinea Pig Model

The auditory midbrain implant (AMI) is a new treatment for hearing restoration in patients with neural deafness or surgically inaccessible cochleae who cannot benefit from cochlear implants (CI). This includes neurofibromatosis type II (NF2) patients who, due to development and/or removal of vestibular schwannomas, usually experience complete damage of their auditory nerves. Although the auditory brainstem implant (ABI) provides sound awareness and aids lip-reading capabilities for these NF2 patients, it generally only achieves hearing performance levels comparable with a single-channel CI. In collaboration with Cochlear Ltd. (Lane Cove, Australia), we developed a human prototype AMI, which is designed for electrical stimulation along the well-defined tonotopic gradient of the inferior colliculus central nucleus (ICC). Considering that better speech perception and hearing performance has been correlated with a greater number of discriminable frequency channels of information available, the ability of the AMI to effectively activate discrete frequency regions within the ICC may enable better hearing performance than achieved by the ABI. Therefore, the goal of this study was to investigate if our AMI array could achieve low-threshold, frequency-specific activation within the ICC, and whether the levels for ICC activation via AMI stimulation were within safe limits for human application. We electrically stimulated different frequency regions within the ICC via the AMI array and recorded the corresponding neural activity in the primary auditory cortex (A1) using a multisite silicon probe in ketamine-anesthetized guinea pigs. Based on our results, AMI stimulation achieves lower thresholds and more localized, frequency-specific activation than CI stimulation. Furthermore, AMI stimulation achieves cortical activation with current levels that are within safe limits for central nervous system stimulation. This study confirms that our AMI design is sufficient for ensuring safe and effective activation of the ICC, and warrants further studies to translate the AMI into clinical application.Minoo Lenarz and Hubert H. Lim contributed equally as first authors.     

Intracortical microstimulation induced changes in spectral and temporal response properties in cat auditory cortex

Intracortical microstimulation (ICMS), consisting of a 40 ms burst (rate 300 Hz) of 10 microA pulses, repetitively administered once per second, for a total duration of 1 h, induced cortical reorganization in the primary auditory cortical field of the anesthetized cat. Multiple single-unit activity was simultaneously recorded from three to nine microelectrodes. Spiking activity was recorded from the same units prior to and following the application of ICMS in conjunction with tone pips at the characteristic frequency (CF) of the stimulus electrode. ICMS produced a significant increase in the mean firing rate, and in the occurrence of burst activity. There was an increase in the cross-correlation coefficient (R) for unit pairs recorded from sites distant from the ICMS site, and a decrease in R for unit pairs that were recorded at the stimulation site. ICMS induced a shift in the CF, dependent on the difference between the baseline CF and the ICMS-paired tone pip frequency. ICMS also resulted in broader tuning curves, increased driven peak firing rate and reduced response latency. This suggests a lasting reduction in inhibition in a small region surrounding the ICMS site that allows expansion of the frequency range normally represented in the vicinity of the stimulation electrode.