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.     

Neuronal responses in chinchilla auditory cortex after postnatal exposure to frequency-modulated tones

Early postnatal exposure to an abnormal acoustic environment has been shown to significantly influence the behaviour of neurons in the auditory cortex. In the present study, we ask if sustained neonatal exposure to an FM sweep affects the development of responses to tonal and FM stimuli in chinchilla auditory cortex. Newborn chinchilla pups were exposed continuously to an upward linear FM sweep (0.1-20 kHz) at 0.05 kHz/ms for 4 weeks. Neuronal responses to pure tones and bidirectional linear FM sweeps (range: 0.1-20 kHz; speeds: 0.05-0.82 kHz/ms) were assessed in anesthetized animals following the exposure period as well as in age-matched controls (P28). We hypothesized that constant FM exposure would increase the response selectivity of cortical neurons to the environmental FM sweep. However, our results show that while tonal response latencies increased after the exposure period (p < 0.0001, one-way ANOVA), the exposure stimulus had minimal effect on neuronal direction sensitivity and decreased neuronal selectivity for any of the presented FM sweep speeds (p < 0.05, one-way ANOVA). We therefore suggest that the development of FM direction sensitivity is experience-independent while normal acoustic experience may be required to maintain FM speed tuning.     

Tonotopic organization of the human auditory cortex probed with frequency-modulated tones

Using neuromagnetic source imaging, we investigated tonotopic representation and direction sensitivity in the auditory cortex of humans (N = 15). For this purpose, source analysis was undertaken at every single sampling point during the presentation of a frequency-modulated tone (FM) sweeping slowly downward or upward across periods of 3 s duration. Stimuli were selected to target response properties of the central part of the primary auditory cortical field, which has been shown to exhibit sensitivity to distinct FM-sound features as compared to the ventral and dorsal part. Linear mixed-effects model statistics confirm tonotopic gradients in medial-lateral and anterior-posterior directions. The high resolution provided by this method revealed that the relationship between frequency and spatial location of the responding neural tissue is nonlinear. The idea that neurons specifically sensitive to the employed sound characteristics (slow, downward modulation) were activated is supported by the fact that the upward sweep of identical duration produced a different pattern of functional organisation.     

Divergent response properties of layer-V neurons in rat primary auditory cortex

Layer-V pyramidal cells comprise a major output of primary auditory cortex (A1). At least two cell types displaying different morphology, projections and in vitro physiology have been previously identified in layer-V. The focus of the present study was to characterize extracellular receptive field properties of layer-V neurons to determine whether a similar breakdown of responses can be found in vivo. Recordings from 105 layer-V neurons revealed two predominant receptive field types. Thirty-two percent displayed strong excitatory V/U-shaped receptive field maps and spiking patterns with shorter stimulus-driven interspike intervals (ISIs), reminiscent of the bursting cells discussed in the in vitro literature. V/U-shaped maps remained relatively unchanged across the three sequential repetitions of the map run on each neuron. Neurons with V/U-shaped maps were also easily depolarized with extracellular current pulse stimulation. In contrast, 47% of the neurons displayed Complex receptive field maps characterized by weak and/or inconsistent excitatory regions and were difficult to depolarize with current pulses. These findings suggest that V/U-shaped receptive fields could correspond to previously described intrinsic bursting (IB) cells with corticotectal projections, and that neurons with Complex receptive fields might represent the regular spiking (RS) cells with their greater inhibitory input and corticocortical/corticostriatal projection pattern.     

Phase-locked responses to pure tones in the primary auditory cortex

At the level of the brainstem, precise temporal information is essential for some aspects of binaural processing, while at the level of the cortex, rate and place mechanisms for neural coding seem to predominate. However, we now show that precise timing of steady-state responses to pure tones occurs in the primary auditory cortex (AI). Recordings were made from 163 multi-units in guinea pig AI. All units increased their firing rate in response to pure tones at 100 Hz and 46 (28%) gave sustained responses which were synchronised with the stimulus waveform (phase-locking). The phase-locking units were clustered together in columns. Phase-locking was generally strongest in layers III and IV but was also recorded in layers I, II and V. Good phase-locking was observed over a range of 60-250 Hz: some units (30%) were narrow band while others (37%) were low-pass (33% were not determined). Phase-locking strength was also influenced by sound level: some units showed monotonic increases in strength with level and others were non-monotonic. Ten of the units provided a good temporal representation of the fundamental frequency (270 Hz) of a guinea pig vocalisation (rumble) and may be involved in analysing communication calls.     

Relating cluster and population responses to natural sounds and tonal stimuli in cat primary auditory cortex

Most information about neuronal properties in primary auditory cortex (AI) has been gathered using simple artificial sounds such as pure tones and broad-band noise. These sounds are very different from the natural sounds that are processed by the auditory system in real world situations. In an attempt to bridge this gap, simple tonal stimuli and a standard set of six natural sounds were used to create models relating the responses of neuronal clusters in AI of barbiturate-anesthetized cats to the two classes of stimuli. A significant correlation was often found between the response to the separate frequency components of the natural sounds and the response to the natural sound itself. At the population level, this correlation resulted in a rate profile that represented robustly the spectral profiles of the natural sounds. There was however a significant scatter in the responses to the natural sound around the predictions based on the responses to tonal stimuli. Going the other way, in order to understand better the non-linearities in the responses to natural sounds, responses of neuronal clusters were characterized using second order Volterra kernel analysis of their responses to natural sounds. This characterization predicted reasonably well the amplitude of the response to other natural sounds, but could not reproduce the responses to tonal stimuli. Thus, second order non-linear characterizations, at least those using the Volterra kernel model, do not interpolate well between responses to tones and to natural sounds in auditory cortex.     

Maturational aspects of periodicity coding in cat primary auditory cortex.

The click-following responses for single units in the primary auditory cortex of the cat were explored as a function of age. Recordings were obtained in kittens from 9-53 days of age and assembled in four age groups; 10-15 days, 16-21 days, 22-27 days and 30-60 days. Age group means were compared to results obtained in adult cats. The stimulus consisted of one second long click trains presented every three seconds with click rates ranging from 1-32 clicks per second. The response was characterized by entrainment, rate Modulation Transfer Function (rMTF), vector strength (VS) and temporal Modulation Transfer Function (tMTF). Maturational effects on periodicity coding comprised changes in overall responsiveness as well as click-rate dependent changes. The number of spikes elicited by single stimuli increased on average 3-fold between the second post-natal week and adulthood, probably as a result of more efficient synapses in the central auditory pathway and some improvement in thresholds. Adaptation became less pronounced with age; neurons started to respond to the later clicks in the 8/s and 16/s click trains from the third post natal week on. By the end of the first post-natal month the click following responses resembled the adult ones qualitatively, however, increased firing rates and spontaneous rates together with rebound responses continued to produce quantitative differences between the 30-60 days olds and the adults. Limiting rates for the tMTF (50% of the response at 1/s) increased from 6 Hz in the 10-15 day old to 12 Hz in adults. The decrease in the duration of the post-activation suppression coupled with the increased response with age to trains with higher click rates suggested that the maturation of inhibitory processes in the cortex play a major role in this rate dependence.     

Spatial sensitivity of neurons in the anterior, posterior, and primary fields of cat auditory cortex

We assessed the spatial-tuning properties of units in the cat's anterior auditory field (AAF) and compared them with those observed previously in the primary (A1) and posterior auditory fields (PAF). Multi-channel, silicon-substrate probes were used to record single- and multi-unit activity from the right hemispheres of alpha-chloralose-anesthetized cats. Spatial tuning was assessed using broadband noise bursts that varied in azimuth or elevation. Response latencies were slightly, though significantly, shorter in AAF than A1, and considerably shorter in both of those fields than in PAF. Compared to PAF, spike counts and latencies were more poorly modulated by changes in stimulus location in AAF and A1, particularly at higher sound pressure levels. Moreover, units in AAF and A1 demonstrated poorer level tolerance than units in PAF with spike rates modulated as much by changes in stimulus intensity as changes in stimulus location. Finally, spike-pattern-recognition analyses indicated that units in AAF transmitted less spatial information, on average, than did units in PAF-an observation consistent with recent evidence that PAF is necessary for sound-localization behavior, whereas AAF is not.     

Neurons in the cat's primary auditory cortex distinguished by their responses to tones and wide-spectrum noise

In the cortex of barbiturate-anesthetized cats, area AI was identified by its tonotopic organization, and single neurons in that field were examined with regard to the shapes of their spike count-versus-intensity functions, the organization of their frequency-intensity response areas, and their responses to wide-spectrum noise, using calibrated sealed stimulating systems. Neurons whose pure tone rate intensity functions were monotonic in shape displayed V-shaped response areas that were open-ended at high tone intensities. In contrast, cells displaying nonmonotonic tone intensity functions tended to have circumscribed response areas; these cells were responsive to tones over limited ranges of both frequency and intensity. Monotonic neurons almost always responded to wide-spectrum noise stimuli, while nonmonotonic neurons often did not. The mean minimum latent period of monotonic cells (14.0 ms) was significantly shorter than that for nonmonotonic neurons (19.1 ms). For those cells that responded to both tones and noise, minimum latent periods for the two stimuli were similar or identical. Monotonic neurons tended to be horizontally segregated from nonmonotonic neurons across AI's middle cortical layers. The implications of these data for the nature of some neural mechanisms underlying the stimulus selectivity of cortical cells are discussed.     

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.     

Rate and synchronization measures of periodicity coding in cat primary auditory cortex.

Periodicity coding was studied in primary auditory cortex of the ketamine anesthetized cat by simultaneously recording with two electrodes from up to 6 neural units in response to one second long click trains presented once per 3 s. Trains with click rates of 1, 2, 4, 8, 16 and 32/s were used and the responses of the single units were quantified by both rate measures (entrainment and rate modulation transfer function, rMTF) and synchronization measures (vector strength VS and temporal modulation transfer functions, tMTF). The rate measures resulted in low-pass functions of click rate and the synchrony measures resulted in band-pass functions of click rate. Limiting rates (-6 dB point of maximum response) were in the range of 3-24 Hz depending on the measure used. Best modulating frequencies were in the range of 5-8 Hz again depending on the synchrony measure used. It appeared that especially the VS was highly sensitive to spontaneous firing rate, duration of the post click suppression and the size of the rebound response after the suppression. These factors were dominantly responsible for the band-pass character of the VS-rate function and the peak VS frequency was nearly identical to the inverse of the suppression period. It is concluded that the use of the VS and to a lesser extent also the tMTF as the sole measure for the characterization of periodicity coding is not recommended in cases where there is a strong suppression of spontaneous activity. The combination of entrainment and tMTF appeared to characterize the periodicity coding in an unambiguous way.     

Neuronal responses in cat primary auditory cortex to natural and altered species-specific calls

We investigated how natural and morphed cat vocalizations are represented in primary auditory cortex (AI). About 40% of the neurons showed time-locked responses to major peaks in the vocalization envelope, 60% only responded at the onset. Simultaneously recorded multi-unit (MU) activity of these peak-tracking neurons on separate electrodes was significantly more synchronous during stimulation than under silence. Thus, the representation of the vocalizations is likely synchronously distributed across the cortex. The sum of the responses to the low and high frequency part of the meow, with the boundary at 2.5 kHz, was larger than the neuronal response to the natural meow itself, suggesting that strong lateral inhibition is shaping the response to the natural meow. In this sense, the neurons are combination-sensitive. The frequency-tuning properties and the response to amplitude-modulated tones of the MU recordings can explain the responses to natural, and temporally and spectrally altered vocalizations. Analysis of the mutual information in the firing rate suggests that the activity of at least 95 recording sites in AI would be needed to reliably distinguish between the nine different vocalizations. This suggests that a distributed representation based on temporal stimulus aspects may be more efficient than one based on firing rate.     

Neural selectivity for interaural frequency disparity in cat primary auditory cortex.

Single-unit responses to interaural frequency disparities (IFDs) were examined in 74 neurons in cat primary auditory cortex (AI). Thirty-three of these cells were classified as EE (binaural facilitators), 39 were classified as EI (binaural inhibitors), and 2 were classified as EO (binaural occluders). The best frequency (BF) was presented to the dominant (usually the contralateral) ear while tones of the same or different frequency (either higher or lower than BF) were presented simultaneously to the nondominant (usually the ipsilateral) ear. Most cells displayed sensitivity to IFDs and thus were classified according to the IFD condition that elicited the strongest facilitatory or inhibitory response. The stimulus condition which evoked the strongest binaural response is referred to as the best IFD. For 50 cells (68%), the best IFD response was obtained when tones of different frequency were presented to each ear. Across the entire sample, binaural IFD responses of cortical neurons were categorized into one of three groups: Those preferring a lower frequency than BF in the ipsilateral ear (referred to as the 'lower IFD group'), those preferring a frequency equal to BF (the 'zero IFD group'), or those preferring a frequency higher than BF (the 'higher IFD group'). Among EE cells, approximately one third were maximally facilitated when the ipsilateral ear frequency was lower than BF, one third when it was equal to BF, and one third when it was higher than BF. Among EI cells, 50% exhibited deepest inhibition for higher IFDs with relatively fewer cells showing inhibition for zero or lower IFDs. Overall, EI cells responded over a broader range of IFD conditions than EE cells. Finally, approximately 50% of all units exhibited bimodal responses such that cells classified as EE displayed some inhibitory response characteristics when stimulated with certain IFD conditions and vice versa.     

Modelling the response of auditory midbrain neurons in the grassfrog to temporally structured monaural stimuli

In a previous paper [Van Stokkum and Gielen, Hear. Res. 41, 71-86, 1989] a model was presented to describe the processing of monaural stimuli by the auditory periphery of the grassfrog. The main components of this model were: a middle ear filter, transduction and tuning of the haircell, short-term adaptation, action potential (event) generation with refractory properties, and spatiotemporal integration of converging inputs. The model is now extended to model auditory midbrain neurons as third order neurons. The mechanisms that generate selectivity for temporal characteristics of sound are adaptation, coincidence detection of second order neurons, temporal integration of third order neurons, and most important, event generation of the first, second and third order model neurons. Variation of the parameters of the model successfully reproduces the range of response patterns which have been obtained from eighth nerve fibres, dorsal medullary nucleus neurons, and torus semicircularis neurons without inhibition. With a single set of parameters the output of the model in response to a set of spectrally and temporally structured stimuli qualitatively resembles the responses of a single neuron to all these stimuli. In this way the responses to the different stimuli are synthesized into a framework, which functionally describes the neuron.     

Stimulus dependence of spectro-temporal receptive fields in cat primary auditory cortex

The frequency-tuning curve is a static representation of the neuron's sensitivity to stimulus frequency. The temporal aspects of the frequency sensitivity can be captured in the spectro-temporal receptive field (STRF), often presented as the average spectrogram of the stimulus preceding a spike but also as the average frequency-dependent post-stimulus time histogram (PSTH). The temporal envelope of the stimulus produces considerable smoothing, and as a consequence the PSTH representation is finer-grained than the spectrogram representation. Here we compare STRFs for 1/s and 20/s single-frequency stimuli with 120/s steady-state multi-frequency stimuli for 87 recording sites in primary auditory cortex of cats. For the 672 estimated STRFs, which for multi-frequency stimuli were mostly obtained at 55 dB SPL, we found lateral inhibition in 17% of the cases, in 32% post-activation suppression, and in 51% only excitation. In 35% of the recordings the excitatory frequency-tuning curves were very similar for single and multi-frequency stimuli, in the remaining 65% the common finding was the emergence of an intensity independent bandwidth for the multi-frequency stimuli. Comparison of the 20/s and 120/s stimuli showed that the resulting increase in inhibition was strongest in the center of the STRF.     

Stimulus induced and spontaneous rhythmic firing of single units in cat primary auditory cortex.

Recordings were made under ketamine anesthesia from 385 neurons in primary auditory cortex in adult cat and from 265 neurons in 10-55 day old kittens. The temporal Modulation Transfer Function for the response to repetitive click stimuli peaked at 8 Hz. After a click a suppression period of 130- 155 ms in duration, depending on click-rate, was observed. This suppression period limited the response to high click rates and thereby determined the 'resonance' in the click response. The suppression duration in kittens decreased in exponential fashion toward the adult value with a time constant of about 1 month. After the one second duration click-trains an oscillatory rebound with a mean period of 113 ms was observed in about 60% of the recordings in the adult cat. Spontaneous activity showed in about 30% of the neurons an oscillatory autocorrelogram with an average period of 126 ms in the adult cats and 170 ms in kittens.     

Measuring and modelling the response of auditory midbrain neurons in the grassfrog to temporally structured binaural stimuli

The combined selectivity for amplitude modulation frequency (AMF) and interaural time difference (ITD) was investigated for single units in the auditory midbrain of the grassfrog. Stimuli were presented by means of a closed sound system. A large number of units was found to be selective for AMF (95%) or ITD (85%) and mostly, these selectivities were intricately coupled. At zero ITD most units showed a band-pass (54%) or bimodal (24%) AMF-rate histogram. At an AMF of 36 Hz, which is equal to the pulse repetition rate of the mating call, 70% of the units possessed an asymmetrical ITD-rate histogram, whereas about 15% showed a symmetrically peaked histogram. With binaural stimulation more units appeared to be selective for AMF (95%) as was the case with monaural stimulation (85%). A large fraction of the units appeared to be most selective for ITD at AMFs of 36 and 72 Hz, whereas units seldomly exhibited ITD selectivity with unmodulated tones. Based upon previous papers (Melssen et al., 1990; Van Stokkum, 1990) a binaural model is proposed to explain these findings. An auditory midbrain neuron is modelled as a third order neuron which receives excitatory input from second order neurons. Furthermore the model neuron receives inputs from the other ear, which may be either excitatory or inhibitory. Spatiotemporal integration of inputs from both ears, followed by action potential generation, produces a combined selectivity for AMF and ITD. In particular the responses of an experimentally observed EI neuron to a set of stimuli are reproduced well by the model.     

Trials with the auditory response cradle. 1--Neonatal responses to auditory stimuli

The Auditory Response Cradle enables physiological response measures to be recorded from the neonate. Auditory responses are detected in the form of head rotation, startle, body activity and respiration changes. This paper reports the results of trials with 203 neonates using 250 and 1000 Hz pure tone and broad band noise stimuli. Response criteria are determined and spontaneous control 'responses' compared with those resulting from stimulus presentation. The response rate is correlated with the measured intra-meatal sound pressure level. Clear response thresholds are determined for all three stimuli. The sharpness of these motor thresholds is discussed and found to have significant implications for cost-effective neonatal auditory screening.     

Representation of amplitude modulation in the auditory cortex of the cat. II. Comparison between cortical fields

The responses of neuronal clusters to amplitude-modulated tones were studied in five auditory cortical fields of the anesthetized cat: the primary auditory field (AI), second auditory field (AII), anterior auditory field (AAF), posterior auditory field (PAF) and the ventro-posterior auditory field (VPAF). Modulation transfer functions (MTFs) for amplitude-modulated tones were obtained at 172 cortical locations. MTFs were constructed by measuring firing rate (rate-MTFs) and response synchronization (synchronization-MTFs) to sinusoidal and rectangular waveform modulation of CF-tones. The MTFs were characterized by their 'best-modulation frequency' (BMF) and a measure of their quality of 'sharpness' (Q2dB). These characteristics were compared for the five fields. Rate and synchronization MTFs for sinusoidal and rectangular modulation produced similar estimates of BMF and Q2dB. Comparison of averaged BMFs between the cortical fields revealed relatively high BMFs in AAF (mean: 31.1 Hz for synchronization to sinusoidal AM) and moderately high BMFs in AI (14.2 Hz) whereas BMFs encountered in AII, VPAF and PAF were generally low (7.0, 5.2, and 6.8 Hz). The MTFs were relatively broadly tuned (low Q2dB) in AAF and sharper in a low modulation group containing AII, PAF and VPAF. The ventro-posterior field was the most sensitive to changes in the modulation waveform. We conclude that there are significant differences between auditory cortical fields with respect to their temporal response characteristics and that the assessment of these response characteristics reveals important aspects of the functional significance of auditory cortical fields for the coding and representation of complex sounds.     

Frequency specificity of the auditory brain stem response to bone-conducted tones in infants and adults.

Auditory brain stem responses were obtained from normal-hearing infants and adults in response to bone-conducted 500 and 2000 Hz tones presented in quiet and high-pass noise masking. The tones were presented at 70 (500 and 2000 Hz) and 46 (2000 Hz) dB peak to peak equivalent (re: 1 dyne RMS). The high-pass noise-masked waveforms were subtracted in succession to obtain derived responses, providing estimates of the cochlear regions contributing to the nonmasked responses. Findings indicate that the auditory brain stem response to bone-conducted 500 Hz tones is frequency specific for both infants and adults. For 2000 Hz tones, the results show maximum amplitudes for cochlear regions representing the nominal frequency of the tone for adults. For infants, maximum response amplitudes for the derived responses to 2000 Hz, 70 dB tones were obtained within 1/2 octave of the nominal frequency (1410-2000 Hz). Wave V latencies of the derived responses are similar for both groups for 2000 Hz tones, but shorter for infants to 500 Hz tones, supporting the hypothesis that low-frequency bone-conducted stimuli are effectively more intense in infants than adults.