Acta physiol. scand. 1975. 93. 318-335 From the Department of Physiology, University of Helsinki, Finland

Detection of Natural Complex Sounds by Cells in the Primary Auditory Cortex of the Cat BY ANSI R. A. S O V I J ~ ~ R V I Received 13 August 1974

Abstract SOVIJARVI, A. R. A. Detection of complex sounds by cells in the primary auditory cortex of the cat. Acta physiol. scand. 1975. 93. 318-335. The neural mechanisms involved in the detection of natural complex sounds were studied by recording single-neuron responses from 132 cells in the primary auditory cortex of the cat. The cats were paralyzed and under neuroleptanalgesia (NLA). The cells were first stimulated with pure tones; the responses were then compared with those evoked by many different types of complex sounds, most of which were animal vocalizations. Per-stimulus-time (PST) histograms constructed from the responses to repetitive stimuli were compared with the corresponding sound spectrograms formed from the sounds used as stimuli. Of 100 cells 68 per cent gave predictable responses to complex sounds on the basis of their responses to different pure tone frequencies. In 32 per cent of the cells the responses were unpredictable. Half of these cells did not react to pure tones at all but responded to one or more animal vocalizations or generator sounds with different patterns. Some cells reacted to pure tones in quite a different way than to certain complex sounds, e.g. with inhibition instead of excitation. These results indicate that cells in the primary auditory cortex of the cat reacting in an unpredictable way to sounds with a complex structure have a more or less specialized function, in detecting and analyzing natural and other complex sound patterns. Cells reacting phasically to pure tones seem to be involved in the detection of transient sound elements. Key words Cat-Auditory cortex-Unit activity-sound discrimination-Complex sounds

Ablation studies have indicated that a special role of the auditory cortex is to encode complex auditory signals (Diamond and Neff 1957, Goldberg and Neff 1961, Kelly and Whitfield 1971, Cowey and Dewson 1972). Earlier single-neuron recordings have also supported that theory. The auditory cortex in the cat contains neurons which respond specifically to frequency modulated sounds, (Whitfield and Evans 1965, Goldstein et al. 1968, Suga 1968) and to certain complex tone combinations (Katsuki et al. 1962, Feher and Whitfield 1966, Abeles and Goldstein 1972) as well as to combinations of frequency and amplitude modulation (Watanabe 1972) or to the “shape” of amplitude modulated noise (Swarbrick and Whitfield 1972). Moreover, in monkeys a few cells have been shown to respond only to monkey vocalizations with specific acoustic properties, but the responses 318

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319

were not always dependent on simple acoustic features (Funkenstein et al. 1971, Wollberg and Newman 1972, Newman and Wollberg 1973, Winter and Funkenstein 1973). The papers cited above give rise to assume that some neurons in the auditory cortex could have specialized functional properties in detecting of complex sounds that are not simply frequency or amplitude modulated tones but have a more complex structure. Therefore, in this study a systematic search has been made in the primary auditory cortex of the cat for cells with properties that could be used for detection and analysis of different kinds of temporally complex sound patterns. All neurons were first tested with pure tones and subsequently with a set of many different types of complex sounds, most of which were animal vocalizations. Also species-specific vocalizations were used. The predictability of the responses of a neuron to complex sounds was determined from its response pattern and range to different pure tone frequencies. Because general anesthetics strongly depress the function of the auditory cortex (Erulkar et al. 1956, Mountcastle et al. 1957, Schlag and Brand 1958, Miller 1971, Noda and Adey 1973) neuroleptanalgesia (NLA) was used in this study (Sovijarvi and Sainio 1972). Parts of the present results have been published earlier as congress abstracts (Sovijarvi 1972, Sovijarvi 1973).

Material and Methods Material

Single-neuron rxordings were made from 132 cells in the primary auditory cortex of 18 adult domestic cats with weights ranging from 1.8 to 4.7 kg. Only healthy cats responding behaviourally to sounds were used. Anesthesia

The form of anaesthesia was neuroleptanalgesia (NLA) combined with muscle relaxation (Sovijarvi and Sainio 1972). NLA was induced by injecting fentanyl, 0.025 mg/kg, and dehydrobenzperidol, 0.8 mg/kg, intramuscularly (ThalamonaP). Muscle relaxation was achieved with Gallamine triethiodide (Flaxedilm) at on initial intramuscular dose of 4 mg/kg. Respiration through an endotracheal tube was artificial. As the experiments generally lasted 12-15 h, additional doses of the drugs were necessary (Sovijarvi and Sainio 1972). A detailed discussion of the methods of the anaesthesia used here is presented in an earlier related paper (Sovijarvi and Hyvarinen 1974). SurgicaI procedures

Surgical procedures employed were the same as those described in the related paper (Sovijarvi and Hyvarinen 1974). The skull was opened over the primary auditory cortex of the right hemisphere with an electric drill. A plexiglas cylinder was fixed around the hole; a hydraulic micromanipulator was attached to the cylinder, which was filled with mineral oil, forming thereby a closed chamber (Davies 1956). Sound generation

Because a sound-proof room with facilities for microelectrode work was not available at the time of this study, the experiments were carried out in a dimly lighted laboratory room, inside a Faraday cage, which was kept as quiet as possible. The sound pressure levels (SPLs) were measured with a Bruel & Kjaer Precision Sound Lvel Meter 2203 supplied with an octave filter set. All the SPL measurements were referred to 0.0002 dyn/cm2. The level of background noise measured in the recording conditions depended on the frequency band; in the bands from 63 to 500 Hz the SPL of noise varied between 25 and 35 dB, and in the bands from 1.0 to 31.5 kHz between 14 and 21 dB. No tape recordings were made during chance noises. The standard SPL for pure tones was 80-85 dB and the peak SPLs of the natural complex sounds varied from 64 d B to 95 dB. When an active cells was found, it was first tested with pure tones in the range of 0.1-20.0 kHz generated with a Wavetek Waveform Generator 155. All the stimulation sounds

ANSSI R. A. SOVIJARVI

were fed to a Goodmans Twinaxiette 8 loudspeaker situated in the midline in front of the cat at a distance of 40 cm. The duration of the pure tones was 4.0 s; it was triggered by a timing circuitry that also generated the trigger pulses used for computer analysis, timed at 0.8 s before the tone. For automatic analysis identical stimuli were repeated a t a rate of I every 8.5 s 12-30 times in succession. Some cells were also tested with complex sounds generated by a Wavetek Sweep Trigger Generator 114. The responses of the auditory cortical cells to complex sounds were compared with their responses t o pure tones by offering a wide selection of natural complex sounds as stimuli. These sounds were selected for their content of the various information-bearing elements that are relevant in auditory communication (see Suga 1972). The types of natural complex sounds used can be classed as follows: 1 ) harmonic-like sounds with o r without frequency modulation (e.g. vocalization of cats). 2) sounds containing short and successive complex sound elements with prominent frequency and amplitude modulation and comprising a wide frequency spectrum (e.g. the songs of the chaffinch and the nightingale), 3) sounds mainly consisting of noise elements (e.g. the call of a lemming). The time patterns of these sounds thus varied from tonal patterns to short rhythmic transients. The natural sounds used were vocalizations of some birds and mammals, which may be familiar to the cat. The standard repertoire consisted of 12 taped vocalizations of 9 species: cat (3 vocalizations), golden oriole, guinea pig, willow ptarmigan, nightingale (2 vocalizations), chaffinch, willow warbler, lemming and barn swallow. All the examples of natural sounds had been taped with a Tandberg 4000 X tape recorder in the tape archives of the Finnish Broadcasting Company. The standard stimulus tape was prepared in such a way that one channel consisted of 17 identical repetitions of 12 vocalizations, and the other channel contained the trigger pulses for computer analysis. These trigger pulses occurred 0.1-0.45 s before the beginning of the sound. During renewals of the same sound the intervals mentioned above were naturally constant. The time intervals between repetitions of vocalization in different series varied from 4 to 6 s. The frequency spectra of the natural sounds used as stimuli were analyzed with the aid of a Voiceprint Sound Spectrograph 4691 A. The shortest components of the vocalizations lasted about 20 msec ( r . g . at the end of the song of the barn swallow), and the longest continuous sound, the vocalization of a cat, took 2.3 s. The frequency area of the natural sounds was in general between 50 Hz and 8.0 kHz. Some manually generated non-specific “odd” sounds were also used as complex stimuli, such as clapping and rubbing of hands, jingling of keys and clinking of glass. Speaking, singing and whistling were sometimes useful as additional stimuli. Recording and dara collection The extracellular recordings with platinum-iridium microelectrodes with the use of a hydraulic micromanipulator, the amplification and discrimination as well as the acoustic and visual monitoring of action potentials, and the collection of data on magnetic tape were carried out as described in the earlier related paper (Sovijlrvi and Hyvarinen 1974). Dala unalysiu Some recordings were filmed from the oscilloscope with a kymograph camera (Grass C 4). Most of the neuronal responses were analyzed off-line with a p-Linc computer programmed to construct per-stimulustinie (PST) histograms of the responses to successive identical stimulus trials. The duration of the samples for analysis was 4.0 s when taped natural sounds were used as stimuli and 8.0 s when pure tones and generator sounds were used. The samples analyzed were thus longer than the stimuli and so the level of spontaneous activity and any “on” and “off” responses could be seen. The number of trials in the analyses varied from 8 to 32. The computed PST histograms were plotted on paper with a Calcomp 565 digital plotter. Each bar in the x-axes of the histograms represents 10 classes. The sound spectrograms (sonagrams) of the complex sounds were photographed on the same time scale as the PST histograms for detailed analysis of the timing of the responses in the PST histograms.

Site of the electrodes During each experiment the penetration points on the surface of the cortex were examined with a stereomicroscope and re-examined with reference to the average pattern of the sulci after decapitation of the animal and fixation of the brain tissue. In 6 animals the areas from which recordings had been made were serially sectioned and stained with Nissl stain for nuclei. From these sections the thickness of the cortex and the shape of the gyrus could be determined. Comparison between the depth coordinates and the thickness of the cortex established that the recordings were made from neurons of the primary auditory cortex. A map of the penetration points is shown in Fig. I .

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I : . . .

Fig. 1. Site of the electrode tracks o n a standard diagram of the auditory cortex in the right hemisphere. The interrupted line indicates the boundary of the primary auditory cortex (A]), according to Woolsey (1960). (ss) supcasylvian sulcus;(esp) posterior ectosylvian sulcus; (esa) anterior ectosylvian sulcus.

ss

. esa

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Results Recordings were made from 132 cells in the primary auditory cortex of the cat. Not all these cells could be tested with the complete sound stimulation programme, which lasted more than one hour, because the activity of some cells could not be recorded for long enough. Thus, 125 cells were adequately tested with pure tones and so could be classified according to their response patterns. In 100 of these cells the response properties to pure tones and complex sounds were compared. General features of neuronal activity in the auditory cortex

In this material only 4 cells showed no activity without acoustic stimuli; the others were firing spontaneously. Among 132 cells examined, 11 (8%) did not react to any of the acoustic stimuli used, although they showed spontaneous activity. Cells with high sponUNIT 1 6 - 1 - 2

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Fig. 2. Photographic records of the responses of cell 16-1-2 to selected pure tones (a-6) and to complex animal sounds (c-g). The upper traces indicate the action potentials of the neuron and the lower traces the oscillograms of the simulataneous stimulus sounds. This figure shows examples of both inhibitory (a) and excitatory (6) responses to pure tones and predictable responses to complex sound patterns. 21 - 7 5 5 8 7 3

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TABLE I. Classification of the response patterns of auditory cortical cells tested with pure tones.

Total number of cells tested 1. Excitatory responses A. Sustained excitation

B. C. D. E.

Partial or adaptive excitation “On”response and excitation “Off” response and excitation “On-off” response and excitation

II. Inhibitory responses A. Sustained inhibition B. Partial o r adaptive inhibition C. “On” response and inhibition D. “Off” response and inhibition E. “On-off” response and inhibition

I l l . Phasic responses only A. “On” response B. “Off“ response C. “On-off” response

Number of cells

Per cent

I25

100

35

28 25

32 2

? *

I 0 0

1

0 0 33

27 7 3 2 10 5

8

6

9 4

2 12 6

1

1

3

2 3

4

IV. More than one response type in different frequency areas

21

17 10

28

22

A. Excitatory and inhibitory response areas 13 8. Different combinations of “on”, “off” and inhibitory responses in 8 different frequency areas V. No response to pure tones

7

taneous activity gave in general better responses to sounds than those with low spontaneous activity. The lability of the response patterns was a feature common to many cells, but other cells, however, gave stable responses to different types of sound stimuli. Many cells tested generated more impulses during the initial part of long stimuli than later, thus showing adaptation to the stimulus. Habituation of the responses to successive presentations of the same stimulus was also common. Almost invariablj, however, “habituated” cell responded readily to a novel stimulus. Responses to pure tones

Response ranges to pure tones were mapped at a sound pressure level of 80-85 dB from 0.1 to 20.0 KHz (see Methods). 15% of the cells tested, the largest group, had narrow Fig. 3. Per-stimulus-time (PST) histograms computed from the responses of cell 40-1-7 to successive trials of pure tones (a and b) and to complex sounds (c-h). The response pattern, consisting of an “on” component followed by inhibition and an “off“ response (a and b), is reflected in a predictable way (exact time-locking) in the response patterns to complex sounds consisting of transient elements (d-h). In this and the following figures the y axes of the histograms indicate the number of neuronal impulses in each time interval class summed from numerous trials, the number of which is indicated above each histogram. The x axes indicate time; the bars represent 10 classes. The pure tone stimuli are presented as a bar, and the frequency of the tone is indicated above each histogram. The frequency spectra of the complex stimulus sounds are shown as sonagrams on the same time scale as the corresponding histograms just above them. The bars in the sonagrams indicate the frequency in kHz. The peak SPL of each stimulus is shown above each histogram in dB.

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response ranges. Cells with response ranges up to 7.5 octaves were also found. 19 cells (22%)had 2, and 2 cells 3 separate response ranges (multiranged cells). Most of the multiranged cells had both inhibitory and excitatory response ranges. Eight cells also had ranges within which the responses were purely phasic. The threshold curves of some cells were measured in 4 expts. Both narrowly and broadly tuned cells were recorded, as well as cells with curves of multiple minima. A wide variety of response patterns to pure tones was found. However, almost every cell could be placed, on the basis of its response pattern, in one of he major groups in Table I. Of the 125 cells classified, 37 (30%) had phasic "on" and "off" components in their response patterns. Phasic responses were much more commonly given by cells that showed inhibition in their responses than by excited cells; only one excited cell showed a response pattern which included phasic elements. Examples of the response types are shown in Fig. 2-4. Predictable responses to complex sounds

68 per cent of the cells tested responded to complex sounds in a way which could be predicted from their responses to pure tones (Table 11). Predicted sustained (non-phasic) responses, excitatory or inhibitory, to tones and complex sounds were obtained from 33 per cent of the cells. Phasic responses to tones and predicted time-locked responses to transient complex sounds were found in 24 per cent of the cells. Of the 100 cells tested 11 per cent gave no response to pure tones or to the complex sounds used. Some examples are presented on the following pages. Cell 16-1-2 (Fig. 2) responded to a 0.25 kHz tone with inhibition and a slight offset burst (a), but had a n excitatory response range from 0.5 kHz to 18.0 kHz (b). Utterances of a crow, consisting of harmonic elements and noise in an area of 0.6-6.0 kHz, evoked inhibition and "off" responses, best seen during the second and third utterances in c.

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TABLE 11. Classification of auditory cortical cells by their responses t o complex sounds and pure tones. Number of cells Total number of cells tested

I. Responses to complex sounds were predictable from the responses to pure tones A. Sustained (non-phasic) responses to pure tones and complex sounds B. Phasic responses to pure tones and time-locked responses to transient complex sounds C. No response to pure tones or complex sounds

Per cent

I00

100

68

68

33

33

24 11

24

II

11. Responses to complex sounds were not predictable from

the responses to pure tones A. No response to pure tones, but a response to specific types of complex sounds a. Specific natural complex. sounds from tape b. “Odd” complex sounds only c. F M sweep and “odd” complex sounds B. No response to complex sounds, but a response to pure tones C. Different types of responses to pure tones and to specific types of complex sounds

32 17

32

17

10 6 1

4 11

4 11

Thus, in this case the inhibitory effect of the low-frequency sound components was stronger than the excitatory effect of the higher frequencies. On the other hand, the vocalization of a wildcat (d), consisting of harmonic components between 0.2 kHz and 5.1 kHz, evoked excitation, not inhibition. But in the terminal part of the sound, where the sound spectrogram revealed noise elements, the function of the cell was inhibited. This inhibition may have been induced by the noise components in the sound, although these were not within the inhibitory range of the cell, as they were in the sounds of the crow (c). However, inhibition only occurred when some sound components were within the inhibitory range. The upward sweeping harmonic sounds of a guinea-pig (e), which contained frequencies only within the excitatory range of the unit, evoked intense excitation with weak habituation during the third utterance. The song of a nightingale (f)also evoked excitation, which was not precisely time-locked, as was that of cells giving phasic responses. The vocalization of a cat (g) produced moderate excitation, as could be predicted; no elements of this sound lay within the inhibitory area of the cell. Cells reacting with “on” or “off“ components to pure tone frequencies gave usually exactly timed response patterns. The best time-locking in the responses to transient sounds was observed in cells which gave both “on” and “off” responses to pure tones, as the responses of cell 40-1-7 in Fig. 3. The response range of this cell was 0.8-18.0 kHz and the responses to pure tones showed inhibition between “on” and “off” components (a and 6). The cat vocalization shown in c evoked an “on” response, inhibition, and a small “off” response. A short excitation in the rising FM part before the end of the sound was found, too. Timelocked responses were evoked by all short sound components, as seen in d-h. The shorter the sound component and the steeper the slope of the frequency, the stronger were the responses of the cell. For instance, the first 40-ms sound component in the song of nightingale

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B in f evoked saharp excitation peak in the histogram, which was not seen in the response pattern of the “off” type cells to the same stimulus. The best activation was evoked by the 20 ms click elements at the end of the song of the barn swallow (g).This cell also gave better timed responses to the song of the chaffinch (h) than “off” type cells. Unpredictable responses to complex sounds Of the 100 cells tested (Table II), 32 responded to complex sounds in a way which was not predicatable from their responses to pure tones. Of these cells, 17 did not show any response to pure tones in the frequency area used (0.1-20.0 kHz) at SPLs of 80-85 dB. 10 cells responded readily to one or several of the taped natural complex sounds but not at all to pure tones. 6 cells reacted only to “odd” complex sounds, such as clapping of hands, jingling of keys, etc. One cell responded both to F M sweeps and to “odd” complex sounds, but did not react to pure tones used. Fig. 5 relates to cell 34-1-6, which did not respond to pure tones at all ( a ) . Neither did the momentary complex sounds of nightingale songs or harmonic vocalizations of cats elicit any clear response. However, the third utterance in the song of a golden oriole (b), which consists of falling harmonic elements, evoked excitation. The song of a willow warbler elicited some good responses locked to the rhythm of the song, as shown in c. This cell did not respond to FM sweeps, but jingling of keys caused rhythmic excitation. The spontaneous activity of this cell decreased during the test period as seen in the histograms (from a to c). Another example of a “complex” cell is shown in Fig. 6. This cell did not react to any of the pure tone frequencies used; an example is shown in a. A rising-falling FM sweep in the range between 0.5 and 7.0 kHz with a duration of 4 s did not evoke any response either, as seen in b. Nor did the natural complex sounds in the standard stimulation programme drive this cell; its spontaneous activity was unaltered by exposure to the harmonic sounds, transients and noise elements in these sounds. For instance, in d the call of a lemming had no effect on the form of the PST histogram. Yet a complex sound produced by the Wavetek generators evoked the vigorous excitation shown in c. This “gurgling” sound included repetitive, steeply rising F M components and falling FM parts in terraces, as seen in the sonagram. Furthermore, these complex components were combined with three pure tone frequencies of 0.1, 0.9 and 1.8 kHz, which, when used alone, did not evoke any response. Four cells responded to certain pure tones but not to any of the complex sounds used. One of these cells is shown in Fig. 7. This cell responded to pure tones in the range of 1.5-2.7 kHz with sustained excitation that was not, however, very intense. A 2.5 kHz tone, which was the characteristic frequency of the cell, evoked the excitation shown in c. But the complex sounds used caused no response, although most of them consisted of frequency elements lying within the response range of the cell ( a and b). Of these 100 cells, 11 gave unpredictable response patterns to complex sounds compared with the patterns of the pure tone responses. Some cells had only excitatory response ranges, but reacted with inhibition to certain complex sounds. On the other hand, some cells gave only inhibitory responses to pure tones but responded with excitation to certain

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UNIT 3 4 - 1 - 6

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Fig. 5 . PST histograms computed from the activity of cell 34-1-6. In CI the cell appears unresponsive to a 3.0 kHz tone stimulus. In b and c the histograms illustrate excitation in response to the songs of a golden oriole and a willow warbler. These sounds also contain frequency elements around 3.0 kHz, as seen from the sonagrams.

sound patterns. Some complex sounds evoked phasic “on” and “off“ responses which were not evoked by any of the pure tones, and vice versa. Cell 40-1-3 (Fig. 4) responded with sustained inhibition in the 1.&11.0 kHz range. The response to the characteristic inhibitory frequency of 3.0 kHz is shown in a. However, only a few complex sounds gave any response at all, and inhibition was not observed in the responses to complex sounds. The songs of the chaffinch and nightingale A caused excitation and an “off” response in an unpredictable way. An example is shown in b. In this response pattern, however, no exact time-locking to transient sounds was seen. As the sonagram shows, the pattern of this nightingale song consists of frequencies which are all within the inhibitory response range of the cell, including 3.0 kHz. The level of spontaneous activity of this cell became lower during the recording period (from a to 6).

Discussion Anesthesia

General anesthetics profoundly depress the cellular function of the cerebral cortex (Mountcastle et al. 1957, Noda and Adey 1973). Hence, they also decrease or abolish the spon-

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Fig. 6. PST histograms from cell 36-2-10. In a a 2.0 kHz tone does not evoke any response. I n b a risingfalling FM sweep in the range of 0.5-7.0 kHz did not alter the histogram. In c clear excitation is evident in the response to a complex generator sound. But, as seen in d, transient and noisy elements forming the utterance of a lemming did not cause any response.

taneous activity of the auditory cortical cells and substantially reduce their responsiveness to acoustic stimuli (Erulkar et al. 1956, Katsuki et at. 1959, Sovijarvi and Sainio 1972). For these reasons general anesthesia was avoided and replaced by neuroleptanalgesia combined with muscle relaxation. This kind of combined anesthesia does not significantly alter the electrical function of the auditory cortex in the cat (Sovijarvi and Sainio 1972), and it was needed for eliminating the painful and disagreeable stimuli produced by the preliminary surgical measures and for keeping the test animal immovable. Acoustic conditions

The experiments were performed in an ordinary laboratory room designed for microelectrode work, with background noise at a higher level than it would be in a sound-proof room (see Methods). The SPLs of the stimuli varied from 65 dB to 95 dB, exceeding the background noise level by 50-75 dB. Thus, the signal-to-noise ratio was sufficient for auditory discrimination. But, as the auditory system has been demonstrated to adapt to stationary noise (see Karja 1968), presumably lack of a sound-proof room does not invalidate the results. Moreover, the background noise level during the experiments was to some extent comparable to the noise level in the natural environment of the cat.

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Fig. 7. PST histograms of the responses of cell 32-1-10 to sound stimuli, showing sustained excitation to a 2.5 kHz pure tone (the characteristic frequency) (c), but no responses to complex sounds which sweep over the characteristic frequency (a and b).

Responses of auditory cortical cells to pure tones Seventy-eight per cent of the spontaneously active cells tested in these experiments responded to pure tones (see Table I). This proportion of tone-sensitive cells was about the same as found by Abeles and Goldstein (1972) in the primary auditory cortex of unanesthetized and paralyzed cats. On the other hand, Evans and Whitfield (1964) reported that only 54 per cent of the cells in the A I on unanesthetized and unrestrained cats responded to pure tones, and Bogdanski and Galambos (1960) obtained a value of 70 per cent. The difference between the present results and those mentioned in the two latter papers could conceivably be due to the differences in the analyzing systems. Phasic “on” and “off” responses and weaker, sustained responses, especially when inhibitory, may sometimes pass unnoticed unless dot displays or per-stimulus-time (PST) histograms are constructed, as was done here. The distribution of the different types of response patterns to pure tones (TableI) displayed some interesting features. Firstly, cells giving excitatory and inhibitory responses were almost equally common (28 and 27 per cent, respectively). Secondly, phasic “on” and “off” responses were mostly combined with inhibiton; only one cell showed phasic patterns with excitation. Thirdly, as many as 30 per cent of the cells tested displayed phasic features in their response patterns. These results confirm previous findings that phasic responses are quite common in the auditory cortex both in cats (Bogdanski and Galambos 1960, Gerstein and Kiang 1964) and in monkeys (Katsuki et al. 1962, Funkenstein et al. 1971). Inhibition or suppression of spontaneous activity by tone stimuli has been reported before; Bogdanski and Galambos

330

ANSSI R. A. S O V I J k V I

(1960) found I5 per cent and Evans and Whitfield (1964) 10 per cent. But in the present study a much higher proportion of cells responding in this way was found, 27 per cent. As

before, the discrepancy is probably due to the difference in the sensitivity of the analyzing system. The stimulation methods and the criteria of classification may, of course, have contributed to the differences in the results. The fact that inhibitory and phasic responses were almost as common as excitatory responses in the auditory cortical cells implies the existence of multiple excitatory-inhibitory interactions. The importance of such interactions in complex sound analysis and in sound localization is obvious. Previous workers have shown that some auditory cortical cells may have different types of response patterns in different frequency areas and at different SPLs (Goldstein et a/. 1968, Abeles and Goldstein 1972). In the present study 17 per cent of the cells tested showed differences in their response patterns when the frequency was different but the SPL was the same (Table I). The same cell might give both excitatory and inhibitory responses in different ranges, sometimes widely separated from each other (Fig. 2). In some cells, however, the change of the response pattern was gradual, especially when phasic responses were combined with inhibition. The cells giving the same or different types of response in several separate response ranges (multiranged cells) all had at least one narrow response range. The same phenomenon was noted by Suga (1964,1965 a, b) in the cells of the inferior colliculus and the auditory cortex of echo-locating bats. Many cells had only one response range, narrow or wide, excitatory, inhibitory or purely phasic. Such response ranges have frequently been observed before (Evans and Whitfield 1964, Oonishi and Katsuki 1965, Abeles and Goldstein 1970). Cells with multiple response ranges of different widths, each range tending to have an individual response pattern, presumably have some connection with the analysis of complex sounds.

The junction of phasic cells in the detection of transient sound patterns As already mentioned, many of the cells studied showed phasic responses to pure tones mostly combined with inhibition. When these phasic cells were tested with complex sounds differing in time structure, but having some or all of their sound energy within the response range of the cell, the following observations were made. Sounds closely resembling pure tones, e.g. harmonic sounds with a vocalic character emitted by cats, excited the cells only at the onset or offset of the stimulus sound but caused inhibition or no response at all during the other parts of the sound, the pattern thus resembling the response to pure tones. When some frequency modulation or noise components were included in the sound, the responses to such components were excitatory. Especially when stimulated with sounds composed of a succession of transient elements or clicks, such as occur in the songs of nightingales, the phasic cells reacted as a rule in an exactly time-locked fashion. The best time-locking to transient sounds was seen in cells responding to pure tones with an “on-off’’ pattern (Fig. 3). In this respect these phasic cells resemble those called “lockers” by de Ribaupierre et al. (1972). On the other hand, cells giving sustained excitation to pure tones did not respond

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synchronously to repetitive transient sound complexes; the timing of their responses was comparatively inaccurate. De Ribaupierre et al. place cells of this kind either in a category they call “groupers”, characterized by loose synchrony, or in a group called “special response patterns”, in which there is no time-locking to repetitive clicks. Such results indicate that the phasic cells in the auditory cortex are involved in detecting the onset and offset of acoustic signals and play a specific role in detecting repetitive momentary sound complexes. Predictable time-locked responses to transient sounds in phasic cells were quite common, being found in 24 per cent of the cells studied (Table 11). Complex sound detection by cells giving sustained (non-phasic) responses to pure tones

a. Predictable function. A high proportion of the cells (33 %) responding to pure tones with sustained excitation or inhibition without phasic components reacted predictably to complex sounds (Table 11). Thus cells reacting with sustained excitation to pure tones in a certain frequency range or ranges were driven by all the types of complex sounds used, provided that at least some of the sound components were within the response ranges of the cell. Cells of this kind, which could be called “general responders” or “simple” cells, usually had high spontaneous activity. This finding is consonant with a report of Wollberg and Newman (1972), who found good responsiveness to all kinds of sound stimuli applied to monkey auditory cortical cells which usually have high spontaneous activity. In the same way, inhibitory cells were found which gave predictable sustained inhibition in response to all complex sounds containing elements within the response range of the cell, However, most inhibitory cells also had phasic components in their response patterns (Table I), and some responded in a selective way to complex sounds. Hence, the proportion of the sustained-inhibitory-response cells that reacted in a predictable way to complex sounds was low. Some cells had both excitatory and inhibitory response ranges without clear phasic components in their response patterns. The detection of complex sounds by these cells was somewhat more complicated. If the sound components were all within a single range, the cell gave responses that were typical of this range. But if the sound consisted of frequency components in both the inhibitory and the excitatory ranges of the cell the type of response depended on how large a proportion of the sound energy was within the inhibitory or excitatory range of the cell, or on other structural features of the sound (see Fig. 2). Presumably, such a predictably responding cell is capable of nonselective detection of those frequency components of a complex sound that are within the frequency range or ranges of the cell. Impulse trains from “simple” cells of this kind might then serve as input to cells in the auditory cortex which have a more complex function in the analysis of acoustic information. b. Unpredictuble function. This study revealed some cells in which spontaneous activity was not affected by any of the complex sound patterns used, but which were driven by pure tones in a certain frequency area (Table I1 and e.g. Fig. 7). An interesting point is that no inhibitory range could be found in these cortical cells. However, inhibitory mechanisms activated by complex properties of the sounds must in some way be involved in un-

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predictable responses of this kind, possibly at subcortical levels. This suggestion is supported by Suga’s (1968) finding that an excitatory response of a cell to the characteristic frequency could be inhibited by another simultaneous tone, the frequency of which was outside the response range of the cell. An excitatory-inhibitory interaction was seen at the cortical level in cells which responded with sustained excitation to the pure tones in a frequency range, but were inhibited by certain complex sound patterns consisting of frequency elements within the excitatory range. Sometimes the situation was reversed; pure tone stimuli caused inhibition and some complex sounds evoked excitatory responses in the same cell (Fig. 4). For some cells the repetition rate of the transient sound complexes was the factor on which the unpredictable inhibition depended: for instance, hand-clapping at a rapid rate sometimes caused total inhibition, but time-locked bursts were generated when the rate was slow. This finding indicates the existence of delayed or conditioned inhibitory mechanisms of the kind recently demonstrated by Abeles and Goldstein (1972) in the auditory cortical cells of the cat. Existence of specialized cells for detection of complex sound patterns

In the present study 8 per cent of the 132 cells tested, although firing spontaneously, did not react in any way to the acoustic stimuli used; they responded neither to pure tones nor to complex sounds. Compared with earlier studies, the proportion of acoustically “silent” cells was lower in the present investigation. Evans and Whitfield (1964) found that 23 per cent, and Bogdanski and Galambos (1960) that 18 per cent of the cells in the auditory cortex were unresponsive to acoustic stimuli in unanesthetized and unrestrained cats. In these investigations, however, complex acoustic stimuli were used only occasionally; thus only a few cells responding specifically to complex sounds could be found. On the other hand, Goldstein et al. (1968), who used only swept tones as complex sound stimuli, found less than 5 per cent of “silent” cells in the primary auditory cortex of cats immobilized with gallamine triethiodide. It seems probable that this muscle relaxant when given without any anesthetics, reduces the proportion of “silent” cells by its activating effect on t h e auditory system (Halpern and Black 1967). In the present study 17 per cent of the cells in the primary auditory cortex responded only to certain complex sounds but not to any of the pure tone frequencies used (Table 11). Most of these functionally complex cells responded to one o r more taped animal vocalizations, which were usually acoustically much alike. But sometimes the effective sounds that gave specific responses had somewhat different frequency spectra (see Fig. 5). N o cells responding only to species-specific vocalizations were found when the cells were tested with cat vocalizations of three different kinds. The situation might have been different if behaving animals had been used. These findings could be compared with the recent results of Funkenstein et al. (1971), Wollberg and Newman (1972), Newman and Wollberg (1973). and Winter and Funkenstein (1973), who studied the responses of monkey auditory cortical cells to species-specific vocalization. They found that 2-3 per cent of the cells gave responses only to some acoustically very similar monkey calls, usually consisting of prominent F M components or a noise spectrum. But they also found some cells which responded exclusively to one or other of two closely similar monkey calls, although responding to certain

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other types of calls also. Although these authors did not use vocalizations of other species and did not test every cell with pure tones, these findings seem to be in according with the present results. The present study likewise revealed cells driven only by certain “odd” complex sounds (Table 11), like jingling of keys or clapping of hands, or in a few cases a rapidly varying complex sound from a sound generator (Fig. 6). These cells were unaffected by complex sounds included in the standard set of taped animal vocalizations. The cells specialized for detection of complex sounds differed in their responses to the same complex sound. In general, however, the effective sound patterns included short steep F M components. The responses of these cells were all excitatory; no cells responding only to complex sounds reacted with inhibition. The present finding that as many as 32 per cent of the cells in the auditory cortex gave unpredictable responses to complex sounds was not unexpected. Almost the same percentage of unpredictable responses (37 %) was reported by Winter and Funkenstein (1973) in their study of the responses of auditory cortical cells in the monkey to species-specific vocalization. The features that might have triggered the function of this kind of specialized cell were amply represented in the sounds used in this study; variable types of frequency and amplitude modulations and tone combinations were often represented in one animal vocalization. All of these factors separately have been shown to be cues for the specific reaction of cells in the auditory cortex (Whitfield and Evans 1965, Goldstein et al. 1968, Suga 1965, Oonishi and Katsuki 1965, Feher and Whitfield 1966, Abeles and Goldstein 1972, Watanabe 1972). It is also likely that not only the structure of the sound but also the rate of repetition might be a critical factor for the function of a cell in the sound detection process. Suggested function of the auditory cortical cells in detection of complex sounds

The present results indicate that many of the cells in the primary auditory cortex of the cat contribute in a specific way to the processing and detection of temporally complex acoustic signals. However, the degree of functional complexity of these cells seems to vary. About two thirds of the cells tested in the present study responded in a predictable way to complex sound patterns. Such cells may be concerned with detecting the type of a sound pattern, conveying the information to higher-order neurons that then discriminate the individual sound patterns. Thus, for instance, cells responding phasically to pure tones were also mostly time-locked to transient sound complexes. The cells that responded in a n unpredictable way to complex sounds may function as higher-order neurons with different degrees of specialization; the neurons with the most selective ability to identify sounds seem to be those which respond only to one or more complex sounds, which may be entirely different in structure. The meaning of the sound probably plays some role in such selective responsiveness. It seems likely that in other auditory areas there are more neurons which play a specialized role in the detection of complex sound patterns, receiving inputs from the primary cortical area as well as from lower levels of the auditory pathway. Here it has been shown that a certain population of cells in the primary auditory cortex has a special role in the detection of complex sounds. As reported in the earlier related paper (Sovijarvi and Hyvarinen 1974), some of these same cells, which responded in a time-locked

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fashion to sound transients, also reacted to directional movements of the sound source. Thus a neuron in the primary auditory cortex is not restricted to functioning in one “complex” way. This study has been supported by a grant from the Finnish Cultural Foundation. This paper is based o n the doctoral thesis of Dr. Sovijarvi entitled: “Single-Neuron Responses to Compled and Moving Sounds in the Primary Auditory Cortex of the Cat“, Institute of Physiology, University of Helsinki, Helsinki 1973.

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