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Large-scale organization of ferret auditory cortex revealed using continuous acquisition of intrinsic optical signals.

We have adapted a new approach for intrinsic optical imaging, in which images were acquired continuously while stimuli were delivered in a series of continually repeated sequences, to provide the first demonstration of the large-scale tonotopic organization of both primary and nonprimary areas of the ferret auditory cortex. Optical responses were collected during continuous stimulation by repeated sequences of sounds with varying frequency. The optical signal was averaged as a function of time during the sequence, to produce reflectance modulation functions (RMFs). We examined the stability and properties of the RMFs and show that their zero-crossing points provide the best temporal reference points for quantifying the relationship between the stimulus parameter values and optical responses. Sequences of different duration and direction of frequency change gave rise to comparable results, although in some cases discrepancies were observed, mostly between upward- and downward-frequency sequences. We demonstrated frequency maps, consistent with previous data, in primary auditory cortex and in the anterior auditory field, which were verified with electrophysiological recordings. In addition to these tonotopic gradients, we demonstrated at least 2 new acoustically responsive areas on the anterior and posterior ectosylvian gyri, which have not previously been described. Although responsive to pure tones, these areas exhibit less tonotopic order than the primary fields.

Acoustic Stimulation↗

Discriminative long-term retention of rapidly induced multiunit changes in the hippocampus, medial geniculate and auditory cortex.

Multiunit activity was chronically recorded in the hippocampus (CA3 field), the magnocellular medial geniculate (MGm) and the auditory cortex (AC) of rats during acquisition (12 daily sessions, 10 trials per session) and long-term retention of differential classical conditioning (tones paired with footshocks). Marked increases of multiunit discharges to CS + presentations were first detected in the MGm (5-10 trials) followed (10-20 trials) by the emergence of discriminative responses in the hippocampus and in the AC. During long-term retention tests, 45 days after the end of conditioning, CS + selective responses were observed in the 3 structures. We propose that learning-induced changes in the conditioned stimulus (CS) sensory pathway can have the same temporal stability as the sensory plasticity observed during development or post injury in adult animals.

Animals↗

Temporal coding in the guinea-pig auditory cortex as revealed by optical imaging and its pattern-time-series analysis.

The neural network structure of a guinea-pig's primary auditory cortex is estimated by applying pattern-time-series analysis to the auditory evoked responses. Spatiotemporal patterns in click-evoked responses, observed by optical recording with voltage-sensitive dye, are analyzed by time series analysis using a multivariable autoregressive (MAR) model. Oscillatory neural activities with a distribution of about 10 approximately 40 Hz in the click-induced evoked responses are found in the cortical response field. The cortical regions where the distributed neural oscillations are generated are identified by pattern-time-series analysis. In addition, two types of cortico-cortical connections, unilateral and bilateral connections between the cortical points, are speculated to be the causes of oscillatory neural activity transfer. It can be said that the so-called synchronized neural oscillation, in the sense of coherency or correlation between the two evoked responses at the oscillatory frequency, does not necessarily represent real cortico-cortical neural connections at the evoked response points.

Animals↗

Thalamocortical afferents of Lorente de Nó: medial geniculate axons that project to primary auditory cortex have collateral branches to layer I.

The injection of anterograde tracers into the ventral division of the medial geniculate body (MGV) of both rats and rabbits labels terminal axons in layer I of auditory cortex as well as the more conventional terminal arbors in layers III/IV. Whether these layer I projections represent a separate lemniscal pathway to the molecular layer or arise as collaterals of axons terminating in III/IV has not been addressed. Focal injections of the anterograde tracers biocytin or biotinylated dextran amine were made into the MGV of young rabbits. Serial section reconstruction of single MGV axons in auditory cortex revealed that layer I axons were collaterals of thalamocortical afferents that formed multiple divergent patches within III/IV. MGV collaterals to layer I often coursed tangentially for several millimeters before terminating. In some cases, the layer I collaterals descended to arborize within a thalamocortical patch in layers III/IV. These results suggest considerable radial and tangential divergence in the auditory thalamocortical pathway and argue for an expanded role for layer I in the processing of specific sensory stimuli.

Afferent Pathways↗

Binaural and commissural organization of the primary auditory cortex of the mustached bat.

In the mustached bat, the primary auditory cortex (AI) can be divided into three subdivisions: the Doppler-shifted constant-frequency processing (DSCF) area, and the anterior (AIa) and posterior (AIp) regions. The DSCF area is composed of two subdivisions: excitatory-excitatory (E-E) and inhibitory-excitatory (I-E). The E-E division is located in the ventral portion of the DSCF area and mainly consists of neurons excited bilaterally, while the I-E division is located in the dorsal portion and mainly consists of neurons which are inhibited by ipsilateral ear stimuli, but excited by contralateral ear stimuli. The E-E division is bilaterally connected by commissural fibers, while the I-E division is not. The AIa and AIp regions have neither E-E neurons nor commissural connections. In the AI of the cat, E-E and I-E neurons form alternating bands which are parallel to the frequency axis. E-E bands are bilaterally connected by commissural fibers, but I-E bands are not. The DSCF area shares a similar functional organization with the AI of the cat.

Acoustic Stimulation↗

Visual stimuli activate auditory cortex in the deaf.

Previous brain imaging studies have demonstrated responses to tactile and auditory stimuli in visual cortex of blind subjects, suggesting that removal of one sensory modality leads to neural reorganization of the remaining modalities. To investigate whether similar 'cross-modal' plasticity occurs in human auditory cortex, we used functional magnetic resonance imaging (fMRI) to measure visually evoked activity in auditory areas of both early-deafened and hearing individuals. Here we find that deaf subjects exhibit activation in a region of the right auditory cortex, corresponding to Brodmann's areas 42 and 22, as well as in area 41 (primary auditory cortex), demonstrating that early deafness results in the processing of visual stimuli in auditory cortex.

Adult↗

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.

Acoustic Stimulation↗

Neuronal responses in cat primary auditory cortex to electrical cochlear stimulation. III. Activation patterns in short- and long-term deafness.

The effects of auditory deprivation on the spatial distribution of cortical response thresholds to electrical stimulation of the adult cat cochlea were evaluated. Threshold distributions for single- and multiple-unit responses from the middle cortical layers were obtained on the ectosylvian gyrus in three groups of animals: adult, acutely implanted animals ("acute group"); adult animals, 2 wk after deafening and implantation ("short-term group"); adult, neonatally deafened animals ("long-term group") implanted after 2-5 years of deafness. For all three groups, we observed similar patterns of circumscribed regions of low response thresholds in the region of primary auditory cortex (AI). A dorsal and a ventral region of low response thresholds were found separated by a narrow, anterior-posterior strip of elevated thresholds. The two low-threshold regions in the acute and the short-term group were arranged cochleotopically. This was reflected in a systematic shift of the cortical locations with minimum thresholds as a function of cochlear position of the radial and monopolar stimulation electrodes. By contrast, the long-term deafened animals maintained only weak or no signs of cochleotopicity. In some cases of this group, significant deviations from a simple tri-partition of the dorsoventral axis of AI was observed. Analysis of the spatial extent of the low-threshold regions revealed that the activated area in acute cases was significantly smaller than the long- and the short-term cases for both dorsal and ventral AI. There were no significant differences in the rostrocaudal extent of activation between long- and short-term deafening, although the total activated area in the short-term cases was larger than in long-term deafened animals. The width of the narrow high-threshold ridge that separated the dorsal and ventral low-threshold regions was the widest for the acute cases and the narrowest for the short-term deafened animals. The findings of relative large differences in cortical response distributions between the acute and short-term animals suggests that the effects observed in long-term deafened animals are not solely a consequence of loss of peripheral innervation density. The effects may reflect electrode-specific effects or reorganizational changes based on factors such as differences in excitatory and inhibitory balance.

Animals↗

Plasticity of frequency organization in auditory cortex of guinea pigs with partial unilateral deafness.

We have examined the effect of restricted unilateral cochlear lesions on the orderly topographic mapping of sound frequency in the auditory cortex of adult guinea pigs. These lesions, although restricted in spatial extent, resulted in a variety of patterns of histological damage to receptor cells and nerve fibres within the cochlea. Nevertheless, all lesions resulted in permanent losses of sensitivity of the cochlear neural output across a limited frequency range. Thirty-five to 81 days after such damage to the organ of Corti, the area of contralateral auditory cortex in which the lesioned frequency range would normally have been represented was partly occupied by an expanded representation of sound frequencies adjacent to the frequency range damaged by the lesion. The thresholds at their new characteristic frequencies (CFs) of clusters of cortical neurones in these regions were close to normal thresholds at those frequencies (mean difference across all animals was 3.8 dB). In a second series of experiments, the responses of neurone clusters were examined within hours of making similar cochlear lesions. It was found that shifts in CF toward frequencies spared by the lesions could occur, but thresholds were greatly elevated compared to normal (mean difference was 31.7 dB in five animals). The emergence of sensitive drive in such regions after prolonged recovery periods in lesioned animals thus suggests that the auditory cortical frequency map undergoes reorganization in cases of partial deafness. Some features of this reorganization are similar to changes reported in somatosensory cortex after peripheral nerve injury, and this form of plasticity may therefore be a feature of all adult sensory systems.

Animals↗

Commissural neurons in layer III of cat primary auditory cortex (AI): pyramidal and non-pyramidal cell input.

The types of layer III neurons in cat primary auditory cortex (AI) projecting to the contralateral AI were studied with horseradish peroxidase or horseradish peroxidase conjugated to wheat germ agglutinin. Injections between the anterior and posterior ectosylvian sulci retrogradely labeled both pyramidal and non-pyramidal somata in contralateral cortical layers III, V, and VI in AI, and in the ventral nucleus of the ipsilateral medial geniculate body. Three-quarters (72%) of the retrogradely labeled cells were found in layer III and one-quarter (28%) lay in layers V and VI. Every part of AI was innervated by commissural neurons. The topographical distribution of the labeled cells varied systematically. Injections in the caudal part of AI labeled cells in the caudal part of the opposite AI, while more rostral injections labeled cells in the contralateral, rostral AI. Injections covering the rostro-caudal extent of AI labeled cells throughout the opposite AI. Each part of AI thus projects most strongly to a contralateral, homotypic area, and less strongly to other, adjacent sectors of AI. The types of labeled cells were distinguished from one another on the basis of size, somatic and dendritic morphology, laminar distribution, and nuclear membrane morphology. Their somatodendritic profiles were compared to, and correlated with, those in Golgi-impregnated material from adult animals. Among the pyramidal cells of origin were small, medium-sized, and large neurons, and star pyramidal cells. The non-pyramidal cells of origin included bipolar and multipolar cells. Thus, at least six of the 12 kinds of neurons, as defined by morphological methods, participate in the interhemispheric pathway. Pyramidal cells comprised 65% of the cells of origin, 14% of the labeled cells in layer III were non-pyramidal, and 21% of the neurons could not be classified. It is unknown if these different types of commissural neurons have the same laminar or cytological targets in AI, or if they represent more than one functional or parallel pathway within AI. In any case, cytologically diverse layer III neurons contribute to the commissural system.

Animals↗

A comparison of monaural and binaural responses to frequency modulated (FM) sweeps in cat primary auditory cortex.

Monaural and binaural single unit responses to frequency-modulated (FM) sweeps were compared in cat primary auditory cortex (AI). Both upward-directed (changing from low to high frequency) and downward-directed (changing from high to low frequency) FM sweeps were presented monaurally and binaurally at five rates of frequency modulation (referred to here as the speed of FM sweep). Two types of binaural FM sweep conditions were presented: (1) like-directed FM sweeps, in which identical FM sweeps were presented to both ears, and (2) opposite-directed FM sweeps, in which one ear was presented with one direction of FM sweep while the other ear was simultaneously presented with the opposite direction of FM sweep. In a sample of 78 cells, 33 cells were classified as EE (binaural facilitatory) and 45 were classified as EI (binaural inhibitory). Ninety-four percent of all units were sensitive to the direction and/or speed of FM sweeps. In general, under binaural stimulus conditions, EE cells responded optimally to like-directed FM sweeps, while EI cells preferred opposite-directed FM sweeps. When tested monaurally, 59% of all cells (both EE and EI) were direction selective, with the majority (76%) preferring downward-directed FM sweeps. When tested binaurally, most direction selective EE cells (60%) preferred upward-directed FM sweeps, while the majority of direction selective EI cells (71%) preferred downward-directed FM sweeps. Our analysis also allowed us to classify inhibitory responses of EI cells as either direction selective (37%) or non-direction selective (63%). For FM speed selectivity under monaural conditions, most EE cells preferred fast FM sweep rates (0.4-0.8 kHz/ms), while approximately equal numbers of EI cells preferred either slow (i.e., 0.05-0.1 kHz/ms) or fast (i.e., 0.4-0.8 kHz/ms) speeds. Under binaural conditions, the majority of EE and EI cells responded best to high speeds when tested with like-directed FM sweeps, while the preferred speed with opposite-directed FM sweeps was more broadly tuned. The results suggest the presence of binaural neural mechanisms underlying cortical FM sweep direction and speed selectivity.

Acoustic Stimulation↗

Single-unit selectivity to azimuthal direction and sound pressure level of noise bursts in cat high-frequency primary auditory cortex.

1. The azimuth and sound pressure level (SPL) selectivities of single-unit responses recorded in primary auditory cortex of barbiturate-anesthetized cats were studied by the use of broadband noise bursts delivered in the free field from a moveable loud-speaker. The experiments were carried out with cats located inside a quasianechoic sound-isolation chamber. We studied 71 units with relatively stable response properties. All units were located in the frequency representation between 5.8 and 31 kHz. The data obtained for each unit were displayed as an azimuth-level response area, a contour plot that displays the distribution of response magnitude as a joint function of SPL and azimuth at 0 degrees elevation. From these, azimuth and level functions were obtained to derive descriptors of azimuth and level selectivity. 2. Sensitivity to sound-source azimuth was assessed from the modulation of the average azimuth function (average of azimuth functions obtained to each SPL of noise that was presented) for each unit. The sample was arbitrarily divided into a high-directionality (HD) group (66%) whose average azimuth functions had modulation values of greater than or equal to 75% and a low-directionality (LD) group (34%). The distinction between HD and LD groups was made so that we could analyze the characteristics of units likely to be involved in the representation of sound-source azimuth. 3. There is an overrepresentation of the contralateral sound field and the midline in the sample of HD units. The preferred sector for each unit was defined as the range of azimuths within the frontal sound field throughout which unit response was greater than or equal to 75% of maximum. Each unit was classified as either midline preferring (17%, the midpoint of the preferred sector, i.e., best azimuth, was located within 5 degrees of the midline), contralateral preferring (60%), or ipsilateral preferring (23%). The ratio of contralateral- to ipsilateral-preferring units was 2.5:1. A higher proportion of units had best azimuths located in the 10 degrees sector centered on the midline than in any other 10 degrees sector of the frontal sound field. 4. In one animal, recordings were obtained at seven closely spaced sites in layer IV from single- and multiunit responses, which were narrowly tuned to both azimuth and SPL. The units located along a 1-mm length of an isofrequency strip were tuned to similar frequencies and SPLs but had five distinctly different directional preferences distributed throughout the entire frontal sound field.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustics↗

Effects of ear plugging on single-unit azimuth sensitivity in cat primary auditory cortex. II. Azimuth tuning dependent upon binaural stimulation.

1. Single-unit recordings were carried out in primary auditory cortex (AI) of barbiturate-anesthetized cats. Observations were based on a sample of 131 high-best-frequency (> 5 kHz), azimuth-sensitive neurons. These were identified by their responses to a set of noise bursts, presented in the free field, that varied in azimuth and sound-pressure level (SPL). Each azimuth-sensitive neuron responded well to some levels at certain azimuths, but did not respond well to any level at other azimuths. 2. Unilateral ear plugging was used to infer each neuron's response to monaural stimulation. Ear plugs, produced by injecting a plastic ear mold compound into the external ear, attenuated sound reaching the tympanic membrane by 25-70 dB. The azimuth tuning of a large proportion of the sample (62/131), referred to as binaural directional (BD), was completely dependent upon binaural stimulation because with one ear plugged, these cells were insensitive to azimuth (either responded well at all azimuths or failed to respond at any azimuth) or in a few cases exhibited striking changes in location of azimuth function peaks. This report describes patterns of monaural responses and binaural interactions exhibited by BD neurons and relates them to each cell's azimuth and level tuning. The response of BD cells to ear plugging is consistent with the hypothesis that they derive azimuth tuning from interaural level differences present in noise bursts. Another component of the sample consisted of monaural directional (27/131) cells that derived azimuth tuning in part or entirely from monaural spectral cues. Cells in the remaining portion of the sample (42/131) responded too unreliably to permit specific conclusions. 3. Binaural interactions were inferred by statistical comparison of a cell's responses to monaural (unilateral plug) and binaural (no plug) stimulation. A larger binaural response than either monaural response was taken as evidence for binaural facilitation. A smaller binaural than monaural response was taken as evidence for binaural inhibition. Binaural facilitation was exhibited by 65% (40/62) of the BD sample (facilitatory cells). Many of these exhibited mixed interactions, i.e., binaural facilitation occurred in response to some azimuth-level combinations, and binaural inhibition to others. Binaural inhibition in the absence of binaural facilitation occurred in 35% (22/62) of the BD sample, a majority of which were EI cells, so called because they received excitatory (E) input from one ear (excitatory ear) and inhibitory (I) input from the other (inhibitory ear). One cell that exhibited binaural inhibition received excitatory input from each ear.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Interhemispheric asymmetry of homotopic transcallosal responses of the auditory cortex in the cat].

In majority of 29 immobilized cats under study, the potentials in the right hemisphere had a greater amplitude and shorter latencies than in the left hemisphere when comparing 150-170 symmetrical points in the auditory cortex. The interhemispheric asymmetry depended on the sex of the animals: it was more obvious in females. The maximal asymmetry was observed in pregnant females. The described polarity of transcallosal influences in the auditory cortex seems to be associated with the predominant role of the right hemisphere in organization of spatial hearing.

Animals↗

Cat P300 present after primary auditory cortex ablation.

A long-latency (200-500 msec) endogenous potential with characteristics of the human P300 was recorded over 12 sessions in 4 adult cats. Principal components analysis with t tests showed that this potential was significantly larger in response to rare auditory stimuli than to the same stimuli presented frequently. The primary auditory cortex was ablated bilaterally. The preoperative tone-elicited conditioned eye blink response remained postoperatively. After 12 postoperative sessions, statistical analyses of these data demonstrated that the P300-like potential was still present. Thus, the primary auditory cortex is not necessary for generation of the P300-like response in cats.

Acoustic Stimulation↗

Audiovisual phonological mismatch produces early negativity in auditory cortex.

During silent reading, visual information provided by letters is converted to auditory information in the mind. The purpose of this study was to identify the primary locus for auditory verbal imagery in the brain. Neuromagnetic recording was obtained from 10 right-handed study participants, who were instructed to identify infrequently occurring phonological mismatches between a random-ordered sequence of syllable sounds and a visually presented syllabogram sequence. The activity difference in early latency, calculated by subtracting the averaged responses to matched syllables from the averaged responses to mismatched syllables, showed a spatiotemporal profile strikingly similar to that of mismatch negativity. Auditory imagery of forthcoming verbal sounds may establish a memory trace as a template for imagery-based mismatch negativity generation in the auditory cortex.

Acoustic Stimulation↗

Quantitative assessment of auditory cortex responses induced by imager acoustic noise.

A clustered volume acquisition functional MRI pulse sequence was modified to assess the response to the acoustic noise of echo-planar imaging in the auditory cortex and to determine whether it is possible to obtain data which is relatively free of acoustic contamination. The spatial location and strength (percent signal change) of cortical responses to the imager noise were examined by introducing extra gradient readouts, without slice excitation, to provide acoustic stimulation immediately prior to acquisition of a cerebral volume. The duration of acoustic stimulation was controlled by varying the number of extra gradient readouts. Slice acquisitions were clustered at the end of the repetition time (TR) period to prevent a response from being induced by the volume acquisition itself ("Intra-Acquisition Response"). The cerebral volumes were acquired using a long TR in order to limit the integration of the cortical response across volume acquisitions ("Inter-Acquisition Response"). Cortical responses were observed to be largest and most significant on the medial two-thirds of Heschl's gyrus, the location of primary auditory cortex. Mean signal changes induced by the imager noise were observed to be as high as 0.95%. A 2 sec delay prior to onset of the BOLD response was empirically determined. These results demonstrate that clustered volume acquisitions may be utilized for up to 2 sec of volume acquisition without inducing an appreciable Intra-Acquisition Response and can be used, with a sufficiently long TR, to provide data which are similarly free of any Inter-Acquisition Response.

Adult↗

Musical scale properties are automatically processed in the human auditory cortex.

While listening to music, we immediately detect 'wrong' tones that do not match our expectations based on the prior context. This study aimed to determine whether such expectations can occur preattentively, as indexed by event-related potentials (ERPs), and whether these are modulated by attentional processes. To this end, we recorded ERPs in nonmusicians while they were presented with unfamiliar melodies, containing either a pitch deviating from the equal-tempered chromatic scale (out-of-tune) or a pitch deviating from the diatonic scale (out-of-key). ERPs were recorded in a passive experiment in which subjects were distracted from the sounds and in an active experiment in which they were judging how incongruous each melody was. In both the experiments, pitch incongruities elicited an early frontal negativity that was not modulated by attentional focus. This early negativity, closely corresponding to the mismatch negativity (MMN) of the ERPs, was mainly originated in the auditory cortex and occurred in response to both pitch violations but with larger amplitude for the more salient out-of-tune pitch than the less salient out-of-key pitch. Attentional processes leading to the conscious access of musical scale information were indexed by the late parietal positivity (resembling the P600 of the ERPs) elicited in response to both incongruous pitches in the active experiment only. Our results indicate that the relational properties of the musical scale are quickly and automatically extracted by the auditory cortex even before the intervention of focused attention.

Acoustic Stimulation↗