Neural firing in ventrolateral thalamic nucleus during conditioned vocal behavior in cats.

The ventrolateral (VL) thalamus in mammals is a site well-situated to show vocalization-related neural activity if there is general or classical motor system involvement in vocal production. It receives input from both the basal ganglia and cerebellum, and forms reciprocal connections with motor cortical areas. The current study examined the activity in cat VL thalamus neurons during instrumentally conditioned vocalization. Units in our sample showed irregular spontaneous firing which could be modulated by slowly occurring fluctuations in intensity of vocalization task performance. Two main types of behavioral events were associated with changes in neural firing rate. The first of these was the ingestion of food reward. More than half of all recordings showed phasic bursting patterns during licking; a similar number had increases in firing preparatory to this phasic activity. The second behavioral event modulating unit responses was vocalization. Approximately 60% of recordings showed activity changes time-locked to vocalization. These responses were almost always excitatory, and often involved changes in firing that preceded vocalization onset. No spatial organization of differences in firing pattern between neurons could be distinguished. Our results suggest that VL thalamus may well be involved in mediating vocal behavior, although its functional role remains an object of speculation. Results are compared with previous studies of vocalization-related activity and of VL thalamus activity.

A biomechanical laryngeal model of voice F0 and glottal width control.

A simplified mathematical model of the larynx, based on biomechanical principles, is described. Components represented include cartilages (cricoid, thyroid, arytenoids, and corniculates), muscles (thyroarytenoid [TA], cricothyroid pars rectus [CTR], cricothyroid pars oblique [CTO], posterior cricoarytenoid [PCA], lateral cricoarytenoid [LCA], and transverse arytenoid [TrA]), ligaments (cricoarytenoid [CAL], anterior cricothyroid [ACTL], posterior cricothyroid [PCTL], and vocal ligaments [VL]), and subglottal pressure (PS). Model outputs included equilibrium positions of cartilages, the glottal width, and the estimated fundamental frequency (F0) of vocal fold vibration. Major findings were that TA, CTR, CTO, and TrA all had substantial effects on F0: that PCA caused glottal opening by rotating the arytenoids laterally; that LCA both ventrolaterally translated and medially rotated the arytenoids, producing minimal effects on glottal closure; and that TrA had major effects on glottal closure by dorsomedially translating and medially rotating the arytenoids. The effects of LCA and PCA were generally diminished as activation of other muscles was increased. Muscle activation plots (MAPs) were used to study the effects of independent parametric variation of several muscles on F0 and glottal width. Both of these parameters were found to be under simultaneous control by TA, CTR, CTO, and TrA. LCA and PCA also had some influence on F0 and glottal width contours, but this appeared to be of limited functional significance, since changes in F0 tended to be offset by changes in glottal closure. Finally, the functional significance of rotation and subduction of the cricothyroid joint was examined. It was found that the combination of subduction with rotation provided greatest control and range of Fo as muscle activation was varied systematically. Strengths and limitations of the current model are discussed, future developments are suggested, and implications of model results as constraints for neural modeling efforts are described.

Control of voice F0 by an artificial neural network.

An artificial neural network model is presented which might correspond to one component of fundamental frequency (F0) control by the brain. Good F0 control could be achieved using only seven neurodes. These included three motor neurodes, a single inhibitory neurode influencing only the thyroarytenoid (TA) motor neurode, and three excitatory neurodes, one of which excited all motor neurodes and two of which excited the inhibitory neurode. The potential utility of this type of model in the study of mechanisms of vocal control is discussed.

A quantitative model of voice F0 control.

A mathematical model of the larynx, based on biomechanical principles, is described. Components represented include two cartilage elements (cricoid with locked arytenoids, and thyroid), three muscles (thyroarytenoid [TA], cricothyroid pars rectus [CTr], and cricothyroid pars oblique [CTo]), and two ligaments (cricothyroid and vocal ligaments), as well as subglottal pressure (PS). For any combination of muscle activities and PS level, equilibrium positions and tensions could be calculated for components in the system. The tensions and lengths of vocal fold elements were then used to calculate fundamental frequency (F0) of vocal fold vibration. Systematic variation of model muscle activation and PS patterns allowed study of the behavior of the model. TA activity tended to shorten the vocal folds; increased levels of CTr and CTo activity, and PS, had the opposite effect. Increased activity of any muscle tended to increase vocal fold tension, while PS increases were mainly ineffective. F0 was generally increased by increased CTr, CTo, and PS values. However, TA activity had a strongly nonmonotonic effect on F0. Best control of F0 could be achieved only by a process of co-contraction of all muscles at low frequencies, followed by sustained contraction of CTr and CTo with decreasing TA activity for F0's increasing above this low-frequency range. These results are discussed in terms of their possible implications for norma and abnormal voice production, and as a set of constraints for neural modeling efforts.

Vocalizations in the cat: behavioral methodology and spectrographic analysis.

Attempts to understand the neural mechanisms underlying mammalian vocal behaviors, including speech, require study of the neural activity and anatomy of vocalization-controlling brain structures. Such studies necessitate the application of invasive neurobiological techniques in animal models. In the current study, cats are used in the development of an animal model of vocal tract control. The animals are instrumentally conditioned to vocalize for food reward. Acquisition of this task can occur within a few minutes, although additional training generally is required to solidly establish the behavior and to train subjects to produce consistently high rates of vocalization for prolonged periods of time. Following training, animals can generally sustain a rate of two calls per minute for a period of over two hours. Optimal task performance is partly dependent on motivation level. Although there is considerable variation between animals, the vocalizations produced have an average duration of 600 ms and a fundamental frequency of around 500 Hz. In addition, during a typical vocalization, there are dynamic variations of about 150 Hz for fundamental frequency and 17 dB for sound intensity. These variations provide opportunities for relating neural and muscular activity to different aspects of the vocal behavior they control. Based on a number of considerations, the model and techniques discussed here probably are most applicable to studying the neurobiology of sub-cortical nuclei subserving vocal control. Similar mechanisms might well be present in other species, including humans. Thus, data obtained from study of this model may be applicable to understanding the processes underlying vocal tract control during human speech.

Factors influencing neural activity in parabrachial regions during cat vocalizations.

The parabrachial nucleus in mammals is intimately connected with other vocalization controlling brainstem structures. It, along with ventromedially adjacent structures, also has been identified as the pneumotaxic center, and as such shows strong respiratory related activity in the anesthetized cat. The current study examines the neuronal activity in cat parabrachial regions during production of instrumentally conditioned vocalizations. Most of the units in our sample show considerable activity during periods between vocalizations. For many units, firing rate fluctuates during the respiratory cycle, although apparently not as strongly as reported in the decerebrate cat. Also, there is often strong phasic activity during periods where animals are licking to ingest their food rewards. During the peri-vocalization period, various neural activity patterns can be recorded. Most common is an activity increase during the vocalization itself. Moreover, in some units, this activity increase has an auditory component. A smaller number of units show other activity patterns, including a suppression of activity during vocalization and activity increases preceding the vocalization. Overall, our results suggest that the parabrachial region's involvement in vocal control is quite complex, involving convergence of respiratory, acoustic, vocalization-related, and perhaps somatosensory influences.

Coding of spectral fine structure in the auditory nerve. II: Level-dependent nonlinear responses.

Phase-locked discharge patterns of single cat auditory-nerve fibers were analyzed in response to complex tones centered at fiber characteristic frequency (CF). Signals were octave-bandwidth harmonic complexes defined by a center frequency F and an intercomponent spacing factor N, such that F/N was the fundamental frequency. Parameters that were manipulated included the phase spectrum, the number of components, and the intensity of the center component. Analyses employed Fourier transforms of period histograms to assess the degree to which responses were synchronized to the frequencies present in the acoustic stimulus. Several nonlinearities were observed in the response as intensity was varied between threshold and 80-90 dB SPL. Response nonlinearities were strong for all signals except those with random phase spectra. The most commonly observed nonlinearity was an emphasis of one or more stimulus components in the response. The degree of nonlinearity usually increased with intensity and signal complexity and decreased with fiber frequency selectivity. Half-wave rectification introduced synchronization to the missing fundamental. The strength of the response at the fundamental was related to stimulus crest factor. Signals with low center frequencies and high crest factors often elicited instantaneous discharge rates at the theoretical maximum of pi CF. This suggests that the probability of spike generation approaches one during high-amplitude waveform segments. Response nonlinearity was interpreted as arising from three sources, namely, cochlear mechanics, compression of instantaneous discharge rate, and saturation of average discharge rate. At near-threshold intensities, fibers with high spontaneous rates exhibited responses that were linear functions of stimulus waveshape, whereas fibers with low spontaneous spike rates produced responses that were best described in terms of an expansive nonlinearity.

Descending projections from the superior olivary complex to the cochlear nucleus of the cat.

Subdivisions of the cochlear nuclear complex give rise to a number of discrete projections to certain cell groups of the superior olivary complex and also received substantial descending projections from the periolivary nuclei. In the present study, we sought to determine by means of retrograde transport of horseradish peroxidase (HRP), and anterograde transport of radiolabeled protein, if the periolivary nuclei give rise to discrete projections to the various subdivisions of the cochlear nuclear complex. Following medium to large injections of HRP into the cochlear nucleus, irrespective of location, labeled cells were found in all periolivary nuclei bilaterally. In every case more than 40% of the labeled cells were found in the lateral nucleus of the trapezoid body on the same side and the ventral nucleus of the trapezoid body of both sides. Other periolivary nuclei contributing more than 5% of the total number of cells in individual cases were the contralateral lateral nucleus of the trapezoid body and the ipsilateral anterolateral and dorsal periolivary nuclei. Injections of tritiated leucine into periolivary nuclei gave rise to axonal labeling to the trapezoid body and the dorsal acoustic stria, usually bilaterally, and to terminal labeling that was widely distributed within the cochlear nuclear complex. In several cases with small injections, particularly in the lateral nucleus of the trapezoid body, the projections from the periolivary nuclei to the anteroventral and dorsal cochlear nuclei connected areas described as having similar best-frequency representation. The autoradiographic data corroborated the main results from the HRP experiments and provided additional information permitting these conclusions: the projections from the periolivary nuclei to the cochlear nuclear complex are organized tonotopically, at least in part; each periolivary nucleus (and perhaps individual cells), projects widely throughout the cochlear nuclear complex; the pattern of termination of projections from different periolivary nuclei to a given region of the cochlear nuclear complex are similar, as seen in autoradiograms, and the lateral and dorsal periolivary nuclei project mainly ipsilaterally, while the medial periolivary nuclei project bilaterally with a contralateral bias. The magnitude of these projections and their widespread distribution within the cochlear nuclear complex would suggest an important role for the descending projections in the normal functioning of the cochlear nucleus.

Coding of spectral fine structure in the auditory nerve. I. Fourier analysis of period and interspike interval histograms.

The temporal fine structure of discharge patterns of single auditory-nerve fibers in adult cats was analyzed in response to signals consisting of a variable number of equal-intensity, in-phase harmonics of a common low-frequency fundamental. Two analytic methods were employed. The first method considered Fourier spectra of period histograms based on the period of the fundamental, and the second method considered Fourier spectra of interspike interval histograms (ISIH's). Both analyses provide information about fiber tuning properties, but Fourier spectra of ISIH's also allow estimates to be made of the degree of resolution of individual stimulus components. At low intensities (within 20-40 dB of threshold), indices of synchronization to individual components of complex tones were similar to those obtained for pure tones. This was true even when fibers were capable of responding to several signal components simultaneously. Response spectra obtained at low intensities resembled fibers' tuning curves, and fibers with low spontaneous discharge rates tended to provide better resolution of stimulus components than fibers with high spontaneous rates. Strongly nonlinear behavior existed at higher stimulus intensities. In this, information was transmitted about progressively fewer signal components and about frequencies not present in the acoustic stimulus, and the component eliciting the largest response shifted away from the fiber's characteristic frequency and toward the edges of the stimulus spectrum. This high-intensity "edge enhancement" can result from the combined effects of a compressive input-output nonlinearity, suppression, and the fortuitous addition of internally generated combination tones. The data indicate that sufficient information exists for the auditory system to determine the frequencies of narrowly spaced stimulus components from the temporal fine structure of nerve fiber's responses.

Extraction and enhancement of spectral structure by the cochlea.

The intensity dependence of signal processing in the cat cochlea was studied in responses of single auditory-nerve fibers for harmonic complexes having various amplitude and phase spectra. Analyses were based on information present in temporal discharge cadences, and they consisted of assessing Fourier spectra of period histograms synchronized to the period of the waveform fundamental. At low intensities, response spectra resembled filtered versions of the stimulus spectrum, with the amounts of filtering being determined by fibers' tuning curves. At high intensities, response spectra exhibited nonlinear behavior and could differ dramatically from spectra obtained at low intensities. The high-intensity response typically emphasized one or more aspects of the stimulus spectrum. When the stimulus possessed equal component amplitudes and phases, the features that were emphasized at high intensities were the high- and low-frequency edges of the spectrum, and when the component at fiber CF was changed in phase or amplitude relative to the others, fibers primarily signaled the presence of the phase- or amplitude-shifted component. Many of the intensity-dependent changes in response spectra are accounted for by considering the effects of the compressive input-output nonlinearity operating at or peripheral to the hair-cell level on the temporal waveform.

Suppression of auditory nerve responses. II. Suppression threshold and growth, iso-suppression contours.

Two-tone "synchrony suppression" was studied in responses of single auditory nerve fibers recorded from anesthetized cats. Suppression thresholds for suppressor tones set to a fiber's characteristic frequency (CF) were approximately equal to discharge rate thresholds for CF tones. Suppression thresholds above and below CF were usually lower than the corresponding discharge rate thresholds. However, at all frequencies studied (including CF), suppression thresholds were higher than the corresponding thresholds for discharge synchronization. Across fibers, rates of suppression growth for suppressors at CF were greatest in low-CF fibers and least in high-CF fibers, and there was a systematic decrease in suppression growth rate at CF as CF increased. Within fibers, rates of suppression growth above CF were typically less than at CF, and slopes were monotonically decreasing functions of frequency. Within-fiber rates of suppression growth below CF were variable, but they usually were greater than rates of growth at CF. Iso-suppression contours (frequencies and intensities producing criterion amounts of suppression) indicated that tones near CF are the most potent suppressors at near-threshold intensities, and that the frequency producing the most suppression usually shifts downward as the amount of suppression increases. These data support the notion that synchrony suppression arises primarily as a passive consequence of hair cell activation.

Single-unit responses to cholinergic agents in the rat inferior colliculus.

Single units were recorded from the inferior colliculi of adult male rats anesthetized with urethane. Units were driven with tonal stimuli, and changes in unit responses to the tones were monitored during iontophoretic application of cholinergic drugs. The cholinergic agonists acetylcholine and carbamylcholine potentiated responses in about 50% and suppressed responses in about 35% of units tested. Cholinergic antagonists typically produced effects when delivered alone. Both d-tubocurarine and atropine methyl nitrate excited over 80% of units tested, while mecamylamine and scopolamine inhibited the majority of tested units. Dihydro-beta-erythroidine was generally ineffective. Alpha-bungarotoxin was generally ineffective when delivered alone, but blocked agonist effects. Post-stimulus time histogram (PSTH) patterns, response-intensity functions and response areas were examined for changes during drug delivery. Cholinergic agents did not differentially affect either time periods within the PSTH or frequency bands of response areas, but were especially effective for those intensities producing larger response rates. Taken together with evidence from biochemical studies, our results suggest the presence of a functional cholinergic input into the inferior colliculus which acts to modulate acoustic processing.

Middle and long latency auditory evoked potentials in cat. I. Component definition and dependence on behavioral factors.

Middle (10-50 ms) and long (50-600 ms) latency auditory evoked potentials (AEPs) were investigated in artificially respired, muscle-paralyzed cats. Similarity to human potentials of comparable latencies was examined in two ways: (1) the similarity of waveform features such as peak amplitude, polarity and latency, and (2) the effects of task-related variables on these various waveform features. Four behavioral variations of a classical pupillary conditioning paradigm were used to vary attention and arousal. Twelve peaks and troughs were identified in the AEP: P10, N13, P17, N22, P31, N41, P55, N70, N100, N140, P260 and N520. Principal components analysis (PCA) defined 7 AEP components, some of which spanned several peaks. Analysis both of peak latencies and amplitudes, and of principal component scores, revealed differential effects of the behavioral manipulations on these components: those with latencies longer than 50 ms were strongly influenced by behavioral variations, while earlier components were relatively immune to these effects. On the basis of these findings, several relationships between cat and human AEP components were suggested. Specifically, peaks P10-P41 in the cat were thought related to human middle latency components, cat P55 to human P50, cat N140 to human N300, and cat P260 to human P300. Cat N520 was comparable to several long latency components in humans. No obvious correspondences between cat AEP components and human N90 and P170 were identified.

Middle and long latency auditory evoked potentials in cat. II. Component distributions and dependence on stimulus factors.

The middle (10-50 ms) and long (50-600 ms) latency periods of the auditory evoked potential (AEP) were investigated in muscle-paralyzed, artificially respired cats with respect to two issues: (1) the distribution of components across the skull, and (2) the effects of changing stimulus intensity on component latencies and amplitudes. The distributional data were gathered during a behavioral study in which four behavioral tasks related to classical pupillary conditioning were used to vary attentional and arousal processes. The distributions across the skull surface (averaged across tasks) of 12 peaks and troughs (P10, N13, P17, N22, P31, N41, P55, N70, N100, N140, P260 and N520) and seven principal components derived from the set of waveforms collected during this experiment are reported. Both peak amplitudes and principal component scores were distributed differentially across the skull surface. In the second experiment, acoustic stimulus intensity was varied, and AEPs collected from a vertex and temporal electrode site. In general, increasing stimulus intensity had a stronger influence on the earlier portions of the AEP, where increased amplitude and decreased latency was the rule, than on later ones. The relationships between cat and human AEP components were discussed based on both the data presented in this paper and in previous papers.

ABR measurements in the cat using a forward-masking paradigm.

Probe-elicited wave V amplitudes of the auditory brainstem response (ABR) were measured using a forward-masking paradigm. Subjects were anesthetized cats. For individual experiments, probe frequency and intensity were fixed and masker frequencies and intensities were varied. For each masker frequency, the extent to which the probe-elicited wave V amplitude was reduced by the preceding masker was plotted as a function of masker intensity. The rising segments of the masking functions were fitted with straight lines, using a least-squares procedure, to obtain estimates of their slopes. Masking grew most rapidly for masker frequencies below probe frequency, becoming progressively less steep as masker frequency increased. ABR tuning curves were constructed by using the linear fits to define the masker intensity that caused a 50% reduction in probe-elicited wave V amplitude. The shapes of these tuning curves were comparable to whole-nerve action potential (AP) tuning curves obtained under similar stimulus conditions. These results indicate that ABR amplitude measurements in a forward-masking paradigm can be used to estimate the growth of response to masking stimuli and frequency selectivity in a manner similar to AP amplitude measurements.

Endogenous late positive component of the evoked potential in cats corresponding to P300 in humans.

A long-latency component of the averaged evoked potential recorded from cats was present only when the evoking stimulus was relevant to the task. The amplitude of this component varied inversely with stimulus probability and was independent of stimulus modality.

Progressive changes in energy cost during a three-hour race-walk exercise.

Twenty experienced race-walkers were exercised in a controlled routine walking at 11.6 km/hr continuously for 3 hr, alternately on a treadmill and a cinder track. Analyses of expired air samples taken at 30 min intervals were used to calculate average R.Q. and energy expenditure. R.Q. was found to decrease progressively from 0.92 to 0.66 in the 3 hr and remained at this level 30 min later. The mean energy cost rose from 46.2 to 55.4 kJ/min or 24.7 to 29.7 kJ/min.m2. The results indicate that this group probably experienced an elevation of aerobic activity as they utilized progressively more fat to satisfy metabolic demands and that R.Q. may be a good indicator for determining recovery after severe long duration exercise.