Auditory-evoked potentials to changes in sound duration in urethane-anaesthetized mice.

Spectrotemporally complex sounds carry important information for acoustic communication. Among the important features of these sounds is the temporal duration. An event-related potential called mismatch negativity indexes auditory change detection in humans. An analogous response (mismatch response) has been found to duration changes in speech sounds in rats but not yet in mice. We addressed whether mice show this response, and, if elicited, whether this response is functionally analogous to mismatch negativity or whether adaptation-based models suffice to explain them. Auditory-evoked potentials were epidurally recorded above the mice auditory cortex. The differential response to the changes in a repeated human speech sound /a/ was elicited 53-259 ms post-change (oddball condition). The differential response was observable to the largest duration change (from 200 to 110 ms). Any smaller (from 200 to 120-180 ms at 10 ms steps) duration changes did elicit an observable response. The response to the largest duration change did not robustly differ in amplitude from the response to the change-inducing sound presented without its repetitive background (equiprobable condition). The findings suggest that adaptation may suffice to explain responses to duration changes in spectrotemporally complex sounds in anaesthetized mice. The results pave way for development of a variety of murine models of acoustic communication.

Judging Total Volumes Of Silhouetted Spheres In Different Numerosities.

Volume and number are addressed separately rather than combined in perception research. Yet, our everyday problems often involve summed continuous volumes of countable solid objects with partial depth cues (e.g., food items). The participants were presented with a set of black-and-white silhouettes of spheres that independently varied in numerosity (from 1 to 6) and total volume (2, 4, 6, or 8), and an adjacent silhouette of a partially filled cylinder. They judged how much the silhouetted sphere(s) in the set would raise the level of the cylinder content if the spheres were immersed into that content. Higher total volumes and numerosities of the spheres were judged slower and underestimated. Lower total volumes and numerosities were judged faster and overestimated. These effects strongly reflected the total silhouette area of the spheres in a set. The discontinuous effect of numerosity on judgment accuracy and speed suggested separate judgment modes below and above Numerosity 3.

The release from refractoriness hypothesis of N1 of event-related potentials needs reassessment.

N1 of event-related potentials (ERPs) is augmented in amplitude in ∼50-150 ms by occasional changes (deviants) in the physical features of a sound repeated at intervals of from ∼400 ms to seconds (standard). The release-from-refractoriness hypothesis links the N1 augmentation to a deviant-feature-specific neural population that is fresh to fully respond as opposed to a standard-feature-specific neural population that is unresponsive due to its post-response refractoriness. The present work explored this hypothesis in the context of ERP studies, behavioral habituation studies and studies on stimulus-specific adaptation (SSA). The idea of hundreds of milliseconds neural population-level refractoriness was observed to be founded upon negative N1 evidence (no observable effect of dishabituating stimuli on N1 to standards - the null hypothesis retained) and merely supported by positive N1 evidence (null hypotheses rejected). This idea was also found to be directly challenged by positive N1 evidence. No conclusive network- or single-neuron-level evidence was found for the refractoriness. Therefore, the validity of the release-from-refractoriness hypothesis of N1 to guide psychophysiological research needs reassessment.

Atypical perceptual narrowing in prematurely born infants is associated with compromised language acquisition at 2 years of age.

BACKGROUND: Early auditory experiences are a prerequisite for speech and language acquisition. In healthy children, phoneme discrimination abilities improve for native and degrade for unfamiliar, socially irrelevant phoneme contrasts between 6 and 12 months of age as the brain tunes itself to, and specializes in the native spoken language. This process is known as perceptual narrowing, and has been found to predict normal native language acquisition. Prematurely born infants are known to be at an elevated risk for later language problems, but it remains unclear whether these problems relate to early perceptual narrowing. To address this question, we investigated early neurophysiological phoneme discrimination abilities and later language skills in prematurely born infants and in healthy, full-term infants. RESULTS: Our follow-up study shows for the first time that perceptual narrowing for non-native phoneme contrasts found in the healthy controls at 12 months was not observed in very prematurely born infants. An electric mismatch response of the brain indicated that whereas full-term infants gradually lost their ability to discriminate non-native phonemes from 6 to 12 months of age, prematurely born infants kept on this ability. Language performance tested at the age of 2 years showed a significant delay in the prematurely born group. Moreover, those infants who did not become specialized in native phonemes at the age of one year, performed worse in the communicative language test (MacArthur Communicative Development Inventories) at the age of two years. Thus, decline in sensitivity to non-native phonemes served as a predictor for further language development. CONCLUSION: Our data suggest that detrimental effects of prematurity on language skills are based on the low degree of specialization to native language early in development. Moreover, delayed or atypical perceptual narrowing was associated with slower language acquisition. The results hence suggest that language problems related to prematurity may partially originate already from this early tuning stage of language acquisition.

Numerical discrimination in newborn infants as revealed by event-related potentials to tone sequences.

Humans are able to attentively discriminate number from 6 months of age. However, the age of the emergence of this ability at the pre-attentive stage of processing remains unclear. Event-related potentials (ERPs) were recorded in newborn human infants aged from 3 to 5 days. At 500-ms intervals, the infants were passively exposed to 200-ms sequences of four tones. Each tone could be either 1000 or 1500 Hz in frequency. In most sequences (standards), the ratio of the tones of one frequency to those of the other frequency in a sequence was 2 : 2. In the remaining sequences (deviants, P = 0.1), this ratio was either 3 : 1 or 4 : 0. The mismatch response of ERPs could not be found for 3 : 1 deviants, but it was a robust finding for 4 : 0 deviants, showing the neurophysiological ability of the infants to register the larger deviant-standard difference. The findings suggest very early sensitivity to auditory numerical information in infancy.

Visual mismatch negativity for changes in orientation--a sensory memory-dependent response.

It remains unclear whether the mismatch negativity of event-related potentials (ERPs) in vision resembles its auditory counterpart in terms of memory relatedness. We recorded ERPs to visual bars in adult humans engaged in an auditory task. In one condition, a bar ('standard') repeated at 400- or 1100-ms non-stimulated intervals was rarely (P = 0.1) replaced by another bar of a different orientation ('deviant'). In the other condition (400-ms intervals), the occurrences of the standards were replaced by 10 (P = 0.1 each) bars of different orientations, including that of the deviant ('control-deviant'). Deviants shifted ERPs towards negative polarity relative to standards in occipital electrodes and towards positive polarity in frontal electrodes at 185-205 ms post-stimulus but only when 400-ms non-stimulated intervals were applied. Furthermore, the shift existed even relative to ERPs to control-deviants. The findings suggest that, as in audition, vision supports the detection of voluntarily unattended changes per se within the constraints of sensory memory. The findings also pave the way for the future exploration of both intact and impaired memory-based visual processing and memory capacity.

Effects of an NMDA-receptor antagonist MK-801 on an MMN-like response recorded in anesthetized rats.

In the human brain, auditory sensory memory has been extensively studied using a well-defined component of event-related potential named the mismatch negativity (MMN). The MMN is generated in the auditory and frontal cortices in response to deviant stimuli. In monkeys, cortical N-methyl-d-aspartate (NMDA) receptors have a central role in the generation of the MMN. MMN-like responses have also been recorded in other animals, including rats. The present study aimed at determining whether the MMN-like response in rats depends on an intact NMDA-receptor system. We recorded auditory evoked responses during an oddball paradigm epidurally in anesthetized rats that had received intraperitoneal injections of saline or an NMDA-receptor antagonist MK-801. An MMN-like response was recorded in the oddball paradigm in saline-treated rats. Further, this response was dose-dependently blocked by MK-801. These results suggest that the MMN-like response in rats depends on an intact NMDA-receptor system.

Mismatch negativity reflects numbers of tones of specific frequencies in humans.

The human brain can automatically quantify objects and events. The mismatch negativity (MMN) of the event-related potential (ERP) was recently found to reflect one such ability in the auditory modality. The present study aimed to further validate the finding. ERPs were recorded in adult humans who passively listened to a series of 300-ms sequences of tones. The sequences occurred at 300-ms silent intervals. They comprised a total of six tones that each was either 440 or 660 Hz in frequency. MMN was found for a rare 4:2 ratio interspersed with a frequent 3:3 ratio between the tones of the different frequencies in a sequence, suggesting the ability of the human brain to preattentively discriminate numbers of sounds of specific frequencies at least at a 3:2 ratio.

Preperceptual human number sense for sequential sounds, as revealed by mismatch negativity brain response?

Humans and some other species can nonlinguistically operate on the quantities of things or events, including sounds. Whether this ability is restricted to conscious percepts of sounds developing in approximately 200 ms is, however, unclear. To this end, we recorded the mismatch negativity (MMN) brain response, an index of preperceptual auditory change detection, of adult humans who passively listened to rare sequences of four 50-ms tones ("deviants") interspersed among frequently repeated tones ("standards"). Each tone was either 1000 or 1500 Hz in frequency. Deviants differed from standards in a ratio of the tones of the 2 frequencies. MMN was found for deviants by 160 ms from the onset of their largest ratio difference from standards (2:2 vs. 4:0), suggesting some ability of the human brain to operate on the number of sequential sounds of specific frequencies at a preperceptual time scale.

Proactive interference in a two-tone pitch-comparison task without additional interfering tones.

Two-tone pitch-comparison tasks typically comprise several successive pairs of successive tones separated by silent intervals. The serial occurrence of such pairs has been associated with degraded task performance, but the nature of this association is not fully understood. Human adult participants were presented with successive pairs of successive tones. The latter, to-be-compared tone of a pair could differ from the former, to-be-remembered tone of 1046.5 Hz by no more than +/-15 Hz (25 cents). The direction of this difference was easier to identify when it was opposite to that of the preceding pair than when being the same. Merely responding accordingly (irrespectively of whether the response was correct or not) was found not to account for this finding. Our study demonstrates proactive interference in a two-tone pitch comparison task as the difficulty to remember when the first tone of the present pair occurred relative to the last tone of the immediately preceding pair.

Memory-based detection of rare sound feature combinations in anesthetized rats.

It is unclear whether the ability of the brain to discriminate rare from frequently repeated combinations of sound features is limited to the normal sleep/wake cycle. We recorded epidural auditory event-related potentials in urethane-anesthetized rats presented with rare tones ('deviants') interspersed with frequently repeated ones ('standards'). Deviants differed from standards either in frequency alone or in frequency combined with intensity. In both cases, deviants elicited event-related potentials exceeding in amplitude event-related potentials to standards between 76 and 108 ms from the stimulus onset, suggesting the independence of the underlying integrative and memory-based change detection mechanisms of the brain from the normal sleep/wake cycle. The relations of these event-related potentials to mismatch negativity and N1 in humans are addressed.

Cooling of the cerebellar interpositus nucleus abolishes somatosensory cortical learning-related activity in eyeblink conditioned rabbits.

Nictitating membrane movement and multiple-unit activity in the somatosensory cortex were recorded from rabbits during paired (N=6) and unpaired (N=5) presentations of a tone conditioned stimulus (CS) and an airpuff unconditioned stimulus (US). A behavioural conditioned response (CR) to the CS and an accompanying neural response in the somatosensory cortex developed only in the paired group. Inactivation of the cerebellar interpositus nucleus abolished both the acquired CR and the accompanying neural response. However, the CS facilitated both behavioural and neural responses to the US during the inactivation. Thus, the absence of the CR could not be accounted for by the general inability of the CS to alter the behaviour constituting the CR or the activity of the somatosensory cortex. These findings suggest that the efferent copy of the signal related to the eyeblink CR is projected from the cerebellum to the cerebral cortical areas of the US modality.

Preattentive and attentive responses to changes in small numerosities of tones in adult humans.

The brain hosts a primitive number sense to non-symbolically represent numerosities of objects or events. Small exact numerosities (~4 or less) can be individuated in parallel. In contrast, large numerosities (more than ~4) can only be approximated. However, whether small numerosities can be approximated without their parallel individuation remains unclear. Parallel individuation is suggested to be an attentive process and numerical approximation an automatic process. We, therefore, tested whether small numerosities can be represented preattentively. We recorded adult humans׳ event-related potentials (ERPs) and behavioral responses to 300-ms sequences of six tones (each of either 440 Hz or 660 Hz in frequency). Mostly, a sequence was of 3 tones of each frequency. Occasionally (P=0.1), the numerosities were 4 and 2 (minor changes) or 5 and 1 (major changes). Mismatch negativity (MMN), but no later attention-related positive-polarity ERPs, was observed to the major but not to the minor changes during a visual non-numerical task. In a following attentive task, behavioral responses even to major changes resulted in a very low hit rates (0.11 for major and 0.023 for minor changes) and yet an above-zero false-alarm rate (0.052). The findings support a view that small numerosities of objects can be automatically approximated independently of their attentive individuation.

Auditory cortical and hippocampal local-field potentials to frequency deviant tones in urethane-anesthetized rats: An unexpected role of the sound frequencies themselves.

The human brain can automatically detect auditory changes, as indexed by the mismatch negativity of event-related potentials. The mechanisms that underlie this response are poorly understood. We recorded primary auditory cortical and hippocampal (dentate gyrus, CA1) local-field potentials to serial tones in urethane-anesthetized rats. In an oddball condition, a rare (deviant) tone (p=0.11) randomly replaced a repeated (standard) tone. The deviant tone was either lower (2200, 2700, 3200, 3700Hz) or higher (4300, 4800, 5300, 5800Hz) in frequency than the standard tone (4000Hz). In an equiprobability control condition, all nine tones were presented at random (p=0.11). Differential responses to deviant tones relative to the standard tone were found in the auditory cortex and the dentate gyrus but not in CA1. Only in the dentate gyrus, the responses were found to be standard- (i.e., oddball condition-) specific. In the auditory cortex, the sound frequencies themselves sufficed to explain their generation. These findings tentatively suggest dissociation among non-contextual afferent, contextual afferent and auditory change detection processes. Most importantly, they remind us about the importance of strict control of physical sound features in mismatch negativity studies in animals.

Reflex facilitation during eyeblink conditioning and subsequent interpositus nucleus inactivation in the rabbit (Oryctolagus cuniculus).

In eyeblink conditioning in the rabbit (Oryctolagus cuniculus), not only is a conditioned response (CR) acquired, but also the original reflex is modified as a function of training. In Experiment 1, by comparing unconditioned responses in unpaired and paired groups, 3 types of reflex facilitation were distinguished. One type was linked to exposure to the unconditioned stimuli (USs) and/or experimental setting. The 2nd type was related to the formation of the memory trace for conditioned eyeblink. The 3rd type was linked to the conditioned stimulus immediately preceding the US in the paired group. In Experiment 2, reversible inactivation of the interpositus nucleus (IPN) abolished the CR and reduced the CR-related reflex facilitation, indicating that the latter depends on the plasticity of the IPN.

The newborn human brain binds sound features together.

To process a stimulus as a holistic entity, the human brain must be able to conjoin its different features. Previous evidence suggests that this ability emerges during the first months of life, implying its considerable dependence on postnatal development. We recorded human newborn (1-3 days of age) electrical brain responses to frequently occurring (standard) sounds and to rarely occurring (deviant) sounds in a series. Responses to deviants differed from those to standards despite the fact that only the combination of sound frequency and intensity could be used as a cue for discriminating between these sound types. Our finding suggests that the human brain is ready for auditory feature binding very soon after birth.

The human brain processes repeated auditory feature conjunctions of low sequential probability.

The human brain is known to preattentively trace repeated sounds as holistic entities. It is not clear, however, whether the same holds true if these sounds are rare among other repeated sounds. Adult humans passively listened to a repeated tone with frequent (standard) and rare (deviant) conjunctions of its three features. Six equiprobable variants per conjunction type were assigned from a space built from these features so that the standard variants (P=0.15 each) were not inseparably traceable by means of their linear alignment in this space. Differential scalp-recorded event-related potentials to deviants indicate that the standard variants were traced as repeated wholes despite their preperceptual distinctiveness and resulting rarity among one another.

Activity in the rabbit somatosensory cortex reflects the active procedural memory trace of a classically conditioned eyeblink response.

Behavioral responses and neural responses in the somatosensory cortex were recorded in nine rabbits during the unpaired and paired treatments of classical eyeblink conditioning with a tone conditioned stimulus (CS) and an airpuff unconditioned stimulus. During the unpaired treatment, neither the behavioral nor neural responses to the CS were observed. During the paired treatment, behavioral conditioned response (CR), accompanied by neural activity, was developed. In well-trained animals occasional failures to elicit the CR were accompanied by an absence of neural responses. Nevertheless, the CS modified the behavioral unconditioned response in paired trials, implying that the CR-failures could not reflect the inability of the CS to modulate the pathways triggering the behavior constituting the CR. Thus, a close link between CR elicitation and somatosensory cortical neural response was established. Our finding suggests that this neural activity to a tone CS during classical eyeblink conditioning reflects an efferent copy of the procedural memory trace.

The human brain processes visual changes that are not cued by attended auditory stimulation.

Event-related potentials (ERPs) to visual stimuli were recorded from the scalp of eight adult humans performing a task in which they counted vowels from a heard story. In the oddball condition, a repeated (standard) light bar of 50 ms in duration was rarely (P = 0.1) replaced by a (deviant) one differing in orientation from the standard. In the control condition, standards were simply omitted from the series and only (alone-) deviants retained. In both conditions, visual stimuli were asynchronous with auditory-task-relevant stimuli. ERPs to deviants significantly differed in amplitude from those to standards in the midline electrodes centrally, parietally and occipitally at 160-200 ms from stimulus onset. Occipitally, such a difference was absent between ERPs to alone-deviants and those to standards. The occipital differential ERPs to deviants, which thus could be found only when standards were present in the series, are discussed in the context of the mismatch negativity (MMN).

Rapid categorization of sound objects in anesthetized rats as indexed by the electrophysiological mismatch response.

It is not known whether animals can, similarly to humans, categorize auditory objects based on an abstract rule in combining their physical features. We recorded local-field potentials from the dura above the primary auditory cortex in urethane-anesthetized rats presented with sound series occasionally violating a rule (e.g., "the higher the frequency, the weaker the intensity"). In a separate control condition, the same frequency and intensity levels were applied in the sound objects, but they obeyed no rule. Responses found selectively to the violations of the rule suggest that an abstract rule was represented in the rat brain, enabling auditory categorization.