Bidirectional Regulation of Innate and Learned Behaviors That Rely on Frequency Discrimination by Cortical Inhibitory Neurons.
ABSTRACT: The ability to discriminate tones of different frequencies is fundamentally important for everyday hearing. While neurons in the primary auditory cortex (AC) respond differentially to tones of different frequencies, whether and how AC regulates auditory behaviors that rely on frequency discrimination remains poorly understood. Here, we find that the level of activity of inhibitory neurons in AC controls frequency specificity in innate and learned auditory behaviors that rely on frequency discrimination. Photoactivation of parvalbumin-positive interneurons (PVs) improved the ability of the mouse to detect a shift in tone frequency, whereas photosuppression of PVs impaired the performance. Furthermore, photosuppression of PVs during discriminative auditory fear conditioning increased generalization of conditioned response across tone frequencies, whereas PV photoactivation preserved normal specificity of learning. The observed changes in behavioral performance were correlated with bidirectional changes in the magnitude of tone-evoked responses, consistent with predictions of a model of a coupled excitatory-inhibitory cortical network. Direct photoactivation of excitatory neurons, which did not change tone-evoked response magnitude, did not affect behavioral performance in either task. Our results identify a new function for inhibition in the auditory cortex, demonstrating that it can improve or impair acuity of innate and learned auditory behaviors that rely on frequency discrimination.
Project description:Tinnitus is an auditory disorder, which affects millions of Americans, including active duty service members and veterans. It is manifested by a phantom sound that is commonly restricted to a specific frequency range. Because tinnitus is associated with hearing deficits, understanding how tinnitus affects hearing perception is important for guiding therapies to improve the quality of life in this vast group of patients. In a rodent model of tinnitus, prolonged exposure to a tone leads to a selective decrease in gap detection in specific frequency bands. However, whether and how hearing acuity is affected for sounds within and outside those frequency bands is not well understood. We induced tinnitus in mice by prolonged exposure to a loud mid-range tone, and behaviorally assayed whether mice exhibited a change in frequency discrimination acuity for tones embedded within the mid-frequency range and high-frequency range at 1, 4, and 8 weeks post-exposure. A subset of tone-exposed mice exhibited tinnitus-like symptoms, as demonstrated by selective deficits in gap detection, which were restricted to the high frequency range. These mice exhibited impaired frequency discrimination both for tones in the mid-frequency range and high-frequency range. The remaining tone exposed mice, which did not demonstrate behavioral evidence of tinnitus, showed temporary deficits in frequency discrimination for tones in the mid-frequency range, while control mice remained unimpaired. Our findings reveal that the high frequency-specific deficits in gap detection, indicative of tinnitus, are associated with impairments in frequency discrimination at the frequency of the presumed tinnitus.
Project description:How can we concentrate on relevant sounds in noisy environments? A "gain model" suggests that auditory attention simply amplifies relevant and suppresses irrelevant afferent inputs. However, it is unclear whether this suffices when attended and ignored features overlap to stimulate the same neuronal receptive fields. A "tuning model" suggests that, in addition to gain, attention modulates feature selectivity of auditory neurons. We recorded magnetoencephalography, EEG, and functional MRI (fMRI) while subjects attended to tones delivered to one ear and ignored opposite-ear inputs. The attended ear was switched every 30 s to quantify how quickly the effects evolve. To produce overlapping inputs, the tones were presented alone vs. during white-noise masking notch-filtered ±1/6 octaves around the tone center frequencies. Amplitude modulation (39 vs. 41 Hz in opposite ears) was applied for "frequency tagging" of attention effects on maskers. Noise masking reduced early (50-150 ms; N1) auditory responses to unattended tones. In support of the tuning model, selective attention canceled out this attenuating effect but did not modulate the gain of 50-150 ms activity to nonmasked tones or steady-state responses to the maskers themselves. These tuning effects originated at nonprimary auditory cortices, purportedly occupied by neurons that, without attention, have wider frequency tuning than ±1/6 octaves. The attentional tuning evolved rapidly, during the first few seconds after attention switching, and correlated with behavioral discrimination performance. In conclusion, a simple gain model alone cannot explain auditory selective attention. In nonprimary auditory cortices, attention-driven short-term plasticity retunes neurons to segregate relevant sounds from noise.
Project description:BACKGROUND: Auditory evoked responses can be modulated by both the sequencing and the signal-to-noise ratio of auditory stimuli. Constant sequencing as well as intense masking sounds basically lead to N1m response amplitude reduction. However, the interaction between these two factors has not been investigated so far. Here, we presented subjects tone stimuli of different frequencies, which were either concatenated in blocks of constant frequency or in blocks of randomly changing frequencies. The tones were presented either in silence or together with broad-band noises of varying levels. RESULTS: In silence, tones presented with random sequencing elicited a larger N1m response than tones presented with constant sequencing. With increasing noise level, this difference decreased and even vanished in the condition where noise intensity exceeded the tone intensity by 10 dB. Furthermore, under noisy conditions, the N1m latency was shorter in the constant sequencing condition compared to the random sequencing condition. CONCLUSIONS: Besides the well-known neural habituation mechanisms, bottom-up driven attention plays an important role during auditory processing in noisy environments. This bottom-up driven attention would allow us to track a certain auditory signal in noisy situations without voluntarily paying attention to the auditory modality.
Project description:Stimulus-specific adaptation (SSA) is the specific decrease in the response to a frequent ('standard') stimulus, which does not generalize, or generalizes only partially, to another, rare stimulus ('deviant'). Stimulus-specific adaptation could result simply from the depression of the responses to the standard. Alternatively, there may be an increase in the responses to the deviant stimulus due to the violation of expectations set by the standard, indicating the presence of true deviance detection. We studied SSA in the auditory cortex of halothane-anesthetized rats, recording local field potentials and multi-unit activity. We tested the responses to pure tones of one frequency when embedded in sequences that differed from each other in the frequency and probability of the tones composing them. The responses to tones of the same frequency were larger when deviant than when standard, even with inter-stimulus time intervals of almost 2 seconds. Thus, SSA is present and strong in rat auditory cortex. SSA was present even when the frequency difference between deviants and standards was as small as 10%, substantially smaller than the typical width of cortical tuning curves, revealing hyper-resolution in frequency. Strong responses were evoked also by a rare tone presented by itself, and by rare tones presented as part of a sequence of many widely spaced frequencies. On the other hand, when presented within a sequence of narrowly spaced frequencies, the responses to a tone, even when rare, were smaller. A model of SSA that included only adaptation of the responses in narrow frequency channels predicted responses to the deviants that were substantially smaller than the observed ones. Thus, the response to a deviant is at least partially due to the change it represents relative to the regularity set by the standard tone, indicating the presence of true deviance detection in rat auditory cortex.
Project description:Groupitizing is a recently described phenomenon of numerosity perception where clustering items of a set into smaller "subitizable" groups improves discrimination. Groupitizing is thought to be rooted on the subitizing system, with which it shares several properties: both phenomena accelerate counting and decrease estimation thresholds irrespective of stimulus format (for both simultaneous and sequential numerosity perception) and both rely on attention. As previous research on groupitizing has been almost completely limited to vision, the current study investigates whether it generalizes to other sensory modalities. Participants estimated the numerosity of a series of tones clustered either by proximity in time or by similarity in frequency. We found that compared with unstructured tone sequences, grouping lowered auditory estimation thresholds by up to 20%. The groupitizing advantage was similar across different grouping conditions, temporal proximity and tone frequency similarity. These results mirror the groupitizing effect for visual stimuli, suggesting that, like subitizing, groupitizing is an a-modal phenomenon.
Project description:A detrimental perceptive consequence of damaged auditory sensory hair cells consists in a pronounced masking effect exerted by low-frequency sounds, thought to occur when auditory threshold elevation substantially exceeds 40 dB. Here, we identified the submembrane scaffold protein Nherf1 as a hair-bundle component of the differentiating outer hair cells (OHCs). Nherf1(-/-) mice displayed OHC hair-bundle shape anomalies in the mid and basal cochlea, normally tuned to mid- and high-frequency tones, and mild (22-35 dB) hearing-threshold elevations restricted to midhigh sound frequencies. This mild decrease in hearing sensitivity was, however, discordant with almost nonresponding OHCs at the cochlear base as assessed by distortion-product otoacoustic emissions and cochlear microphonic potentials. Moreover, unlike wild-type mice, responses of Nherf1(-/-) mice to high-frequency (20-40 kHz) test tones were not masked by tones of neighboring frequencies. Instead, efficient maskers were characterized by their frequencies up to two octaves below the probe-tone frequency, unusually low intensities up to 25 dB below probe-tone level, and growth-of-masker slope (2.2 dB/dB) reflecting their compressive amplification. Together, these properties do not fit the current acknowledged features of a hypersensitivity of the basal cochlea to lower frequencies, but rather suggest a previously unidentified mechanism. Low-frequency maskers, we propose, may interact within the unaffected cochlear apical region with midhigh frequency sounds propagated there via a mode possibly using the persistent contact of misshaped OHC hair bundles with the tectorial membrane. Our findings thus reveal a source of misleading interpretations of hearing thresholds and of hypervulnerability to low-frequency sound interference.
Project description:Cochlear filtering results in earlier responses to high than to low frequencies. This study examined potential perceptual correlates of cochlear delays by measuring the perception of relative timing between tones of different frequencies. A brief 250-Hz tone was combined with a brief 1-, 2-, 4-, or 6-kHz tone. Two experiments were performed, one involving subjective judgments of perceived synchrony, the other involving asynchrony detection and discrimination. The functions relating the proportion of "synchronous" responses to the delay between the tones were similar for all tone pairs. Perceived synchrony was maximal when the tones in a pair were gated synchronously. The perceived-synchrony function slopes were asymmetric, being steeper on the low-frequency-leading side. In the second experiment, asynchrony-detection thresholds were lower for low-frequency rather than for high-frequency leading pairs. In contrast with previous studies, but consistent with the first experiment, thresholds did not depend on frequency separation between the tones, perhaps because of the elimination of within-channel cues. The results of the two experiments were related quantitatively using a decision-theoretic model, and were found to be highly correlated. Overall the results suggest that frequency-dependent cochlear group delays are compensated for at higher processing stages, resulting in veridical perception of timing relationships across frequency.
Project description:The mating behaviour of many mosquito species is mediated essentially by sound: males follow and mate with a female mid-flight by detecting and tracking the whine of her flight-tones. The stereotypical rapid frequency modulation (RFM) male behaviour, initiated in response to the detection of the female's flight-tones, has provided a means of investigating these auditory mechanisms while males are free-flying. Mosquitoes hear with their antennae, which vibrate to near-field acoustic excitation. The antennae generate nonlinear vibrations (distortion products, DPs) at frequencies that are equal to the difference between the two simultaneously presented tones, e.g. the male and female flight-tones, which are detected by mechanoreceptors in the auditory Johnston's organ (JO) at the base of the antenna. Recent studies indicated the male mosquito's JO is tuned not to the female flight-tone, but to the frequency difference between the male and female flight-tones. To test the hypothesis that mosquitoes detect this frequency difference, Culex quinquefasciatus males were presented simultaneously with a female flight-tone and a masking tone, which should suppress the male's RFM response to sound. The free-flight behavioural and in vivo electrophysiological experiments revealed that acoustic masking suppresses the RFM response to the female's flight-tones by attenuating the DPs generated in the nonlinear vibration of the antennae. These findings provide direct evidence in support of the hypothesis that male mosquitoes detect females when both are in flight through difference tones generated in the vibrations of their antennae owing to the interaction between their own flight-tones and those of a female.
Project description:Poor discrimination of nonlinguistic sounds has been implicated in language-learning problems in children, but research evidence has been inconsistent. This study included 32 participants with specific language impairment (SLI) and 32 typically developing controls aged 7-16 years. Frequency discrimination thresholds were estimated in a task where participants had to distinguish a higher-frequency tone from a 1000 Hz tone. Neurophysiological responses were assessed in an oddball paradigm. Stimuli were either 1030 or 1200 Hz pure tones (deviants) presented in a series of standard 1000 Hz tones, or syllables (deviant [da] or [bi] in a series of standard /ba/). On the behavioral task, children (7- to 11-year-olds) had high thresholds, regardless of language status, but teenagers (12-16 years) with SLI had higher thresholds than their controls. Conventional analysis of electrophysiological responses showed no difference between groups for the mismatch negativity (MMN), but the late discriminative negativity (LDN) was reduced in amplitude for smaller deviants in participants with SLI. Time-frequency analysis revealed that, whereas the MMN reflected enhanced intertrial coherence in the theta frequency band, the LDN corresponded to a period of event-related desynchronization extending across a wide low-frequency band including delta, theta, and alpha. This manifested as a drop in power in those frequencies, which was marked in the controls but reduced or absent in children with SLI across all stimulus types. This provides compelling evidence for a low-level auditory perceptual impairment in SLI that affects a processing stage after initial detection of a sound change.
Project description:Mice reproduce interesting effects in auditory discrimination learning and knowledge transfer discussed in human studies: (i) the advantage in the transfer from a hard to an easy task by benefits from transfer of procedural knowledge and information-integration learning, and (ii) the disadvantage in the transfer from easy to hard tasks by inability to generalize across perceptually different classes of stimuli together with initially unsuccessful attempts to transfer cognitive skills from one task to the other. House mice (NMRI strain) were trained in a shuttle-box stimulus discrimination task. They had to discriminate either between two pure tones of different frequencies (PT) or between two different modulation frequencies of an amplitude-modulated tone (AM). Then transfer of knowledge between these two tasks was tested. Mice rapidly learned PT discrimination within two to three training sessions (easy task). AM discrimination learning took longer and did not reach the high performance level of PT discrimination (hard task). No knowledge transfer was detected in animals first trained with the easy (PT) followed by the hard (AM) discrimination task. Mice benefited, however, from knowledge transfer when the AM discrimination was followed by the PT discrimination. When the task changed, confusion of conditioned stimuli occurred if the carrier frequency of the AM was the same as one of the frequencies in the PT task. These results show a hard-to-easy effect when possible knowledge transfer is tested between qualitatively different stimulus classes. The data establish mice as promising animal model for research on genetics of auditory perception and learning.