Auditory Research publications

Introduction: Evoked compound action potentials (ECAPs) measured using epidural spinal recordings (ESRs) during epidural spinal cord stimulation (SCS) can help elucidate fundamental mechanisms for the treatment of pain, as well as inform closed-loop control of SCS. Previous studies have used ECAPs to characterize the neural response to various neuromodulation therapies and have demonstrated that ECAPs are highly prone to multiple sources of artifact, including post-stimulus pulse capacitive artifact, electromyography (EMG) bleed-through, and motion artifact resulting from disturbance of the electrode/tissue interface during normal behavior. However, a thorough characterization has yet to be performed for how these sources of artifact may contaminate recordings within the temporal window commonly used to determine activation of A-beta fibers in a large animal model. Methods: We characterized the sources of artifacts that can contaminate the recording of ECAPs in an epidural SCS swine model using the Abbott Octrode™ lead. Muscle paralytics were administered to block muscle activation preventing EMG from contaminating the recorded ECAPs. Concurrent EMG recordings of the longissimus, a long muscle of the back, were used to confirm a 2-4 millisecond (ms) latency source of EMG bleed-through that frequently contaminated the A-beta temporal window. Additionally, we obtained recordings approximately 5-10 minutes post-mortem after clear evoked A-beta and associated EMG responses ceased to characterize the representation of stimulation artifact across the array. Results: Spinal ECAP recordings can be contaminated by capacitive artifact, short latency EMG from nearby long muscles of the back, and motion artifact from multiple sources. In many cases, the capacitive artifact can appear nearly identical in duration and waveshape to evoked A-beta responses. These sources of EMG can have phase shifts across the electrode array, very similar to the phase shift anticipated by propagation of an evoked A-beta fiber response across the array. This short latency EMG is often evident at currents similar to those needed to activate A-beta fibers associated with the treatment of pain. Changes in cerebrospinal fluid between the cord and dura, and motion induced during breathing created a cyclic oscillation in all evoked components of the recorded ECAP signal. Conclusion: Careful controls must be implemented to accurately separate neural signal from the sources of artifact in spinal cord ECAPs. To address this, we suggest experimental procedures and associated reporting requirements necessary to disambiguate the underlying neural response from these confounds. These data are important to better understand the conceptual framework for recorded ESRs, with components such as ECAPs, EMG responses and artifacts, and have important implications for closed-loop control algorithms to account for transient motion such as postural changes and cough.

Hearing is an active process in which listeners must detect and identify sounds, segregate and discriminate stimulus features, and extract their behavioral relevance. Adaptive changes in sound detection can emerge rapidly, during sudden shifts in acoustic or environmental context, or more slowly as a result of practice. Although we know that context- and learning-dependent changes in the spectral and temporal sensitivity of auditory cortical neurons support many aspects of flexible listening, the contribution of subcortical auditory regions to this process is less understood. Here, we recorded single- and multi-unit activity from the central nucleus of the inferior colliculus (ICC) and the ventral subdivision of the medial geniculate nucleus (MGV) of Mongolian gerbils under two different behavioral contexts: as animals performed an amplitude modulation (AM) detection task and as they were passively exposed to AM sounds. Using a signal detection framework to estimate neurometric sensitivity, we found that neural thresholds in both regions improved during task performance, and this improvement was driven by changes in firing rate rather than phase locking. We also found that ICC and MGV neurometric thresholds improved and correlated with behavioral performance as animals learn to detect small AM depths during a multi-day perceptual training paradigm. Finally, we reveal that in the MGV, but not the ICC, context-dependent enhancements in AM sensitivity grow stronger during perceptual training, mirroring prior observations in the auditory cortex. Together, our results suggest that the auditory midbrain and thalamus contribute to flexible sound processing and perception over rapid and slow timescales. Significance statement What a listener hears depends on several factors, such as whether the listener is attentive or distracted, and whether the sound is meaningful or irrelevant. Practice can also shape hearing by improving the detection of particular sound features, as occurs during language or musical learning. Understanding how changes in sound perception are implemented in the brain is important for developing strategies to optimize healthy hearing, and for treating disorders in which these processes go awry. We report that neurons in auditory midbrain and thalamus exhibit rapid shifts in sound sensitivity that depend on the sound’s behavioral relevance, and slower improvements that emerge over several days of training. Our results suggest that subcortical areas make an important contribution to flexible hearing.

Melody is a core component of music in which discrete pitches are serially arranged to convey emotion and meaning. Perception varies along several pitch-based dimensions: (i) the absolute pitch of notes, (ii) the difference in pitch between successive notes, and (iii) the statistical expectation of each note given prior context. How the brain represents these dimensions and whether their encoding is specialized for music remains unknown. We recorded high-density neurophysiological activity directly from the human auditory cortex while participants listened to Western musical phrases. Pitch, pitch-change, and expectation were selectively encoded at different cortical sites, indicating a spatial map for representing distinct melodic dimensions. The same participants listened to spoken English, and we compared responses to music and speech. Cortical sites selective for music encoded expectation, while sites that encoded pitch and pitch-change in music used the same neural code to represent equivalent properties of speech. Findings reveal how the perception of melody recruits both music-specific and general-purpose sound representations.

Introduction Cochlear implants (CIs) are the treatment of choice for severe to profound hearing loss. Variability in CI outcomes remains despite advances in technology and is attributed in part to differences in cortical processing. Studying these differences in CI users is technically challenging. Spectrally degraded stimuli presented to normal-hearing individuals approximate input to the central auditory system in CI users. This study used intracranial electroencephalography (iEEG) to investigate cortical processing of spectrally degraded speech. Methods Participants were adult neurosurgical epilepsy patients. Stimuli were utterances /aba/ and /ada/, spectrally degraded using a noise vocoder (1–4 bands) or presented without vocoding. The stimuli were presented in a two-alternative forced choice task. Cortical activity was recorded using depth and subdural iEEG electrodes. Electrode coverage included auditory core in posteromedial Heschl’s gyrus (HGPM), superior temporal gyrus (STG), ventral and dorsal auditory-related areas, and prefrontal and sensorimotor cortex. Analysis focused on high gamma (70–150 Hz) power augmentation and alpha (8–14 Hz) suppression. Results Chance task performance occurred with 1–2 spectral bands and was near-ceiling for clear stimuli. Performance was variable with 3–4 bands, permitting identification of good and poor performers. There was no relationship between task performance and participants demographic, audiometric, neuropsychological, or clinical profiles. Several response patterns were identified based on magnitude and differences between stimulus conditions. HGPM responded strongly to all stimuli. A preference for clear speech emerged within non-core auditory cortex. Good performers typically had strong responses to all stimuli along the dorsal stream, including posterior STG, supramarginal, and precentral gyrus; a minority of sites in STG and supramarginal gyrus had a preference for vocoded stimuli. In poor performers, responses were typically restricted to clear speech. Alpha suppression was more pronounced in good performers. In contrast, poor performers exhibited a greater involvement of posterior middle temporal gyrus when listening to clear speech. Discussion Responses to noise-vocoded speech provide insights into potential factors underlying CI outcome variability. The results emphasize differences in the balance of neural processing along the dorsal and ventral stream between good and poor performers, identify specific cortical regions that may have diagnostic and prognostic utility, and suggest potential targets for neuromodulation-based CI rehabilitation strategies.

Stimulus-specific adaptation (SSA), the reduction of neural activity to a common stimulus that does not generalize to other, rare stimuli, is an essential property of our brain. Although well characterized in adults, it is still unknown how it develops during adolescence and what neuronal circuits are involved. Using in vivo electrophysiology and optogenetics in the lemniscal pathway of the mouse auditory system, we observed SSA to be stable from postnatal day 20 (P20) in the inferior colliculus, to develop until P30 in the auditory thalamus and even later in the primary auditory cortex (A1). We found this maturation process to be experience-dependent in A1 but not in thalamus and to be related to alterations in deep but not input layers of A1. We also identified corticothalamic projections to be implicated in thalamic SSA development. Together, our results reveal different circuits underlying the sequential SSA maturation and provide a unique perspective to understand predictive coding and surprise across sensory systems.

The auditory steady-state response (ASSR) is a cortical oscillation induced by trains of 40 Hz acoustic stimuli. While the ASSR has been widely used in clinic measurement, the underlying neural mechanism remains poorly understood. In this study, we investigated the contribution of different stages of auditory thalamocortical pathwaymedial geniculate body (MGB), thalamic reticular nucleus (TRN), and auditory cortex (AC)to the generation and regulation of 40 Hz ASSR in C57BL/6 mice of both sexes. We found that the neural response synchronizing to 40 Hz sound stimuli was most prominent in the GABAergic neurons in the granular layer of AC and the ventral division of MGB (MGBv), which were regulated by optogenetic manipulation of TRN neurons. Behavioral experiments confirmed that disrupting TRN activity has a detrimental effect on the ability of mice to discriminate 40 Hz sounds. These findings revealed a thalamocortical mechanism helpful to interpret the results of clinical ASSR examinations. Significance Statement Our study contributes to clarifying the thalamocortical mechanisms underlying the generation and regulation of the auditory steady-state response (ASSR), which is commonly used in both clinical and neuroscience research to assess the integrity of auditory function. Combining a series of electrophysiological and optogenetic experiments, we demonstrate that the generation of cortical ASSR is dependent on the lemniscal thalamocortical projections originating from the ventral division of medial geniculate body to the GABAergic interneurons in the granule layer of the auditory cortex. Furthermore, the thalamocortical process for ASSR is strictly regulated by the activity of thalamic reticular nucleus (TRN) neurons. Behavioral experiments confirmed that dysfunction of TRN would cause a disruption of mice's behavioral performance in the auditory discrimination task.

Human language follows statistical regularities or linguistic laws. For instance, Zipf's law of brevity states that the more frequently a word is used, the shorter it tends to be. All human languages adhere to this word structure. However, it is unclear whether Zipf's law emerged de novo in humans or whether it also exists in the non-linguistic vocal systems of our primate ancestors. Using a vocal conditioning paradigm, we examined the capacity of marmoset monkeys to efficiently encode vocalizations. We observed that marmosets adopted vocal compression strategies at three levels: (i) increasing call rate, (ii) decreasing call duration and (iii) increasing the proportion of short calls. Our results demonstrate that marmosets, when able to freely choose what to vocalize, exhibit vocal statistical regularities consistent with Zipf's law of brevity that go beyond their context-specific natural vocal behaviour. This suggests that linguistic laws emerged in non-linguistic vocal systems in the primate lineage.

Social learning (SL) through experience with conspecifics can facilitate the acquisition of many behaviors. Thus, when Mongolian gerbils are exposed to a demonstrator performing an auditory discrimination task, their subsequent task acquisition is facilitated, even in the absence of visual cues. Here, we show that transient inactivation of auditory cortex (AC) during exposure caused a significant delay in task acquisition during the subsequent practice phase, suggesting that AC activity is necessary for SL. Moreover, social exposure induced an improvement in AC neuron sensitivity to auditory task cues. The magnitude of neural change during exposure correlated with task acquisition during practice. In contrast, exposure to only auditory task cues led to poorer neurometric and behavioral outcomes. Finally, social information during exposure was encoded in the AC of observer animals. Together, our results suggest that auditory SL is supported by AC neuron plasticity occurring during social exposure and prior to behavioral performance.

Direct neural recordings from human auditory cortex have demonstrated encoding for acoustic-phonetic features of consonants and vowels. Neural responses also encode distinct acoustic amplitude cues related to timing, such as those that occur at the onset of a sentence after a silent period or the onset of the vowel in each syllable. Here, we used a group reduced rank regression model to show that distributed cortical responses support a low-dimensional latent state representation of temporal context in speech. The timing cues each capture more unique variance than all other phonetic features and exhibit rotational or cyclical dynamics in latent space from activity that is widespread over the superior temporal gyrus. We propose that these spatially distributed timing signals could serve to provide temporal context for, and possibly bind across time, the concurrent processing of individual phonetic features, to compose higher-order phonological (e.g. word-level) representations.

Understanding central auditory processing critically depends on defining underlying auditory cortical networks and their relationship to the rest of the brain. We addressed these questions using resting state functional connectivity derived from human intracranial electroencephalography. Mapping recording sites into a low-dimensional space where proximity represents functional similarity revealed a hierarchical organization. At a fine scale, a group of auditory cortical regions excluded several higher-order auditory areas and segregated maximally from the prefrontal cortex. On mesoscale, the proximity of limbic structures to the auditory cortex suggested a limbic stream that parallels the classically described ventral and dorsal auditory processing streams. Identities of global hubs in anterior temporal and cingulate cortex depended on frequency band, consistent with diverse roles in semantic and cognitive processing. On a macroscale, observed hemispheric asymmetries were not specific for speech and language networks. This approach can be applied to multivariate brain data with respect to development, behavior, and disorders.

Cortical representations supporting many cognitive abilities emerge from underlying circuits comprised of several different cell types. However, cell type-specific contributions to rate and timing-based cortical coding are not well-understood. Here, we investigated the role of parvalbumin neurons in cortical complex scene analysis. Many complex scenes contain sensory stimuli which are highly dynamic in time and compete with stimuli at other spatial locations. Parvalbumin neurons play a fundamental role in balancing excitation and inhibition in cortex and sculpting cortical temporal dynamics; yet their specific role in encoding complex scenes via timing-based coding, and the robustness of temporal representations to spatial competition, has not been investigated. Here, we address these questions in auditory cortex of mice using a cocktail party-like paradigm, integrating electrophysiology, optogenetic manipulations, and a family of spike-distance metrics, to dissect parvalbumin neurons’ contributions towards rate and timing-based coding. We find that suppressing parvalbumin neurons degrades cortical discrimination of dynamic sounds in a cocktail party-like setting via changes in rapid temporal modulations in rate and spike timing, and over a wide range of time-scales. Our findings suggest that parvalbumin neurons play a critical role in enhancing cortical temporal coding and reducing cortical noise, thereby improving representations of dynamic stimuli in complex scenes.

The perception of pitch is a fundamental percept, which is mediated by the auditory system, requiring the abstraction of stimulus properties related to the spectro-temporal structure of sound. Despite its importance, there is still debate as to the precise areas responsible for its encoding, which may be due to species differences or differences in the recording measures and choices of stimuli used in previous studies. Moreover, it was unknown whether the human brain contains pitch neurons and how distributed such neurons might be. Here, we present the first study to measure multiunit neural activity in response to pitch stimuli in the auditory cortex of intracranially implanted humans. The stimulus sets were regular-interval noise with a pitch strength that is related to the temporal regularity and a pitch value determined by the repetition rate and harmonic complexes. Specifically, we demonstrate reliable responses to these different pitch-inducing paradigms that are distributed throughout Heschl’s gyrus, rather than being localized to a particular region, and this finding was evident regardless of the stimulus presented. These data provide a bridge across animal and human studies and aid our understanding of the processing of a critical percept associated with acoustic stimuli.

In bistable perception, observers experience alternations between two interpretations of an unchanging stimulus. Neurophysiological studies of bistable perception typically partition neural measurements into stimulus-based epochs and assess neuronal differences between epochs based on subjects' perceptual reports. Computational studies replicate statistical properties of percept durations with modeling principles like competitive attractors or Bayesian inference. However, bridging neuro-behavioral findings with modeling theory requires the analysis of single-trial dynamic data. Here, we propose an algorithm for extracting nonstationary timeseries features from single-trial electrocorticography (ECoG) data. We applied the proposed algorithm to 5-min ECoG recordings from human primary auditory cortex obtained during perceptual alternations in an auditory triplet streaming task (six subjects: four male, two female). We report two ensembles of emergent neuronal features in all trial blocks. One ensemble consists of periodic functions that encode a stereotypical response to the stimulus. The other comprises more transient features and encodes dynamics associated with bistable perception at multiple time scales: minutes (within-trial alternations), seconds (duration of individual percepts), and milliseconds (switches between percepts). Within the second ensemble, we identified a slowly drifting rhythm that correlates with the perceptual states and several oscillators with phase shifts near perceptual switches. Projections of single-trial ECoG data onto these features establish low-dimensional attractor-like geometric structures invariant across subjects and stimulus types. These findings provide supporting neural evidence for computational models with oscillatory-driven attractor-based principles. The feature extraction techniques described here generalize across recording modality and are appropriate when hypothesized low-dimensional dynamics characterize an underlying neural system. SIGNIFICANCE STATEMENT Irrespective of the sensory modality, neurophysiological studies of multistable perception have typically investigated events time-locked to the perceptual switching rather than the time course of the perceptual states per se. Here, we propose an algorithm that extracts neuronal features of bistable auditory perception from largescale single-trial data while remaining agnostic to the subject's perceptual reports. The algorithm captures the dynamics of perception at multiple timescales, minutes (within-trial alternations), seconds (durations of individual percepts), and milliseconds (timing of switches), and distinguishes attributes of neural encoding of the stimulus from those encoding the perceptual states. Finally, our analysis identifies a set of latent variables that exhibit alternating dynamics along a low-dimensional manifold, similar to trajectories in attractor-based models for perceptual bistability.

From myriads of ongoing stimuli, the brain creates a fused percept of the environment. This process, which culminates in perceptual binding, is presumed to occur through the operations of multisensory neurons that occur throughout the brain. However, because different brain areas receive different inputs and have different cytoarchitechtonics, it would be expected that local multisensory features would also vary across regions. The present study investigated that hypothesis using multiple single-unit recordings from anesthetized cats in response to controlled, electronically-generated separate and combined auditory, visual, and somatosensory stimulation. These results were used to compare the multisensory features of neurons in cat primary auditory cortex (A1) with those identified in the nearby higher-order auditory region, the Dorsal Zone (DZ). Both regions exhibited the same forms of multisensory neurons, albeit in different proportions. Multisensory neurons exhibiting excitatory or inhibitory properties occurred in similar proportions in both areas. Also, multisensory neurons in both areas expressed similar levels of multisensory integration. Because responses to auditory cues alone were so similar to those that included non-auditory stimuli, it is proposed that this effect represents a mechanism by which multisensory neurons subserve the process of perceptual binding.

Sensory responses typically vary depending on the recent history of sensory experience. This is essential for processes, including adaptation, efficient coding, and change detection. In the auditory cortex (AC), the short-term history dependence of sound-evoked (onset) responses has been well characterized. Yet many AC neurons also respond to sound terminations, and little is known about the history dependence of these "offset" responses, whether the short-term dynamics of onset and offset responses are correlated, or how these properties are distributed among cell types. Here we presented awake male and female mice with repeating noise burst stimuli while recording single-unit activity from primary AC. We identified parvalbumin and somatostatin interneurons through optotagging, and also separated narrow-spiking from broad-spiking units. We found that offset responses are typically less depressive than onset responses, and this result was robust to a variety of stimulus parameters, controls, measurement types, and selection criteria. Whether a cell's onset response facilitates or depresses does not predict whether its offset response facilitates or depresses. Cell types differed in the dynamics of their onset responses, and in the prevalence, but not the dynamics, of their offset responses. Finally, we clustered cells according to spiking responses and found that response clusters were associated with cell type. Each cluster contained cells of several types, but even within a cluster, cells often showed cell type-specific response dynamics. We conclude that onset and offset responses are differentially influenced by recent sound history, and discuss the implications of this for the encoding of ongoing sound stimuli.SIGNIFICANCE STATEMENT Sensory neuron responses depend on stimulus history. This history dependence is crucial for sensory processing, is precisely controlled at individual synapses and circuits, and is adaptive to the specific requirements of different sensory systems. In the auditory cortex, neurons respond to sound cessation as well as to sound itself, but how history dependence is used along this separate, "offset" information stream is unknown. We show that offset responses are more facilitatory than sound responses, even in neurons where sound responses depress. In contrast to sound onset responses, offset responses are absent in many cells, are relatively homogeneous, and show no cell type-specific differences in history dependence. Offset responses thus show unique response dynamics, suggesting their unique functions.

Background: Sensory impairments commonly occur in patients with autism or intellectual disability. Fragile X syndrome (FXS) is one form of intellectual disability that is often comorbid with autism. In electroencephalographic (EEG) recordings obtained from humans with FXS, the ability of cortical regions to consistently synchronize, or "phase-lock", to modulated auditory stimuli is reduced compared to that of typically developing individuals. At the same time, less time-locked, "non-phase-locked" power induced by sounds is higher. The same changes occur in the Fmr1 knockout (KO) mouse - an animal model of FXS. We determined if Fmr1 deletion in a subset of brainstem auditory neurons plays any role in these EEG changes in the mouse. Methods: We reinstated FMRP expression in a subpopulation of brainstem auditory neurons in an otherwise Fmr1 KO control (conditional on; cON Fmr1) mouse and used EEG recordings to determine if reinstatement normalized, or "rescued", the phase-locking phenotype observed in the cON Fmr1 mouse. In determining rescue, this also meant that Fmr1 deletion in the same neuron population was necessary for the phenotype to occur. Results: We find that Fmr1 reinstatement in a subset of brainstem neurons rescues certain aspects of the phase-locking phenotype but does not rescue the increase in non-phase-locked power. Unexpectedly, not all electrophysiological phenotypes observed in the Fmr1 KO were observed in the cON Fmr1 mouse used for the reinstatement experiments, and this was likely due to residual expression of FMRP in these Fmr1 KO controls. Conclusions: Fmr1 deletion in brainstem neurons is necessary for certain aspects of the decreased phase-locking phenotype in the Fmr1 KO, but not necessary for the increase in non-phase-locked power induced by a sound. The most likely brainstem structure underlying these results is the inferior colliculus. We also demonstrate that low levels of FMRP can rescue some EEG phenotypes but not others. This latter finding provides a foundation for how symptoms in FXS individuals may vary due to FMRP levels and that reinstatement of low FMRP levels may be sufficient to alleviate particular symptoms.

Elevated neural plasticity during development contributes to dramatic improvements in perceptual, motor, and cognitive skills. However, malleable neural circuits are vulnerable to environmental influences that may disrupt behavioral maturation. While these risks are well-established prior to sexual maturity (i.e., critical periods), the degree of neural vulnerability during adolescence remains uncertain. Here, we induce transient hearing loss (HL) spanning adolescence in gerbils, and ask whether behavioral and neural maturation are disrupted. We find that adolescent HL causes a significant perceptual deficit that can be attributed to degraded auditory cortex processing, as assessed with wireless single neuron recordings and within-session population-level analyses. Finally, auditory cortex brain slices from adolescent HL animals reveal synaptic deficits that are distinct from those typically observed after critical period deprivation. Taken together, these results show that diminished adolescent sensory experience can cause long-lasting behavioral deficits that originate, in part, from a dysfunctional cortical circuit.

Background To localize sound sources accurately in a reverberant environment, human binaural hearing strongly favors analyzing the initial wave front of sounds. Behavioral studies of this “precedence effect” have so far largely been confined to human subjects, limiting the scope of complementary physiological approaches. Similarly, physiological studies have mostly looked at neural responses in the inferior colliculus, the main relay point between the inner ear and the auditory cortex, or used modeling of cochlear auditory transduction in an attempt to identify likely underlying mechanisms. Studies capable of providing a direct comparison of neural coding and behavioral measures of sound localization under the precedence effect are lacking. Results We adapted a “temporal weighting function” paradigm previously developed to quantify the precedence effect in human for use in laboratory rats. The animals learned to lateralize click trains in which each click in the train had a different interaural time difference. Computing the “perceptual weight” of each click in the train revealed a strong onset bias, very similar to that reported for humans. Follow-on electrocorticographic recording experiments revealed that onset weighting of interaural time differences is a robust feature of the cortical population response, but interestingly, it often fails to manifest at individual cortical recording sites. Conclusion While previous studies suggested that the precedence effect may be caused by early processing mechanisms in the cochlea or inhibitory circuitry in the brainstem and midbrain, our results indicate that the precedence effect is not fully developed at the level of individual recording sites in the auditory cortex, but robust and consistent precedence effects are observable only in the auditory cortex at the level of cortical population responses. This indicates that the precedence effect emerges at later cortical processing stages and is a significantly “higher order” feature than has hitherto been assumed.

Previous psychophysical studies have identified a hierarchy of time-averaged statistics which determine the identity of natural sound textures. However, it is unclear whether the neurons in the inferior colliculus (IC) are sensitive to each of these statistical features in the natural sound textures. We used 13 representative sound textures spanning the space of 3 statistics extracted from over 200 natural textures. The synthetic textures were generated by incorporating the statistical features in a step-by-step manner, in which a particular statistical feature was changed while the other statistical features remain unchanged. The extracellular activity in response to the synthetic texture stimuli was recorded in the IC of anesthetized rats. Analysis of the transient and sustained multiunit activity after each transition of statistical feature showed that the IC units were sensitive to the changes of all types of statistics, although to a varying extent. For example, we found that more neurons were sensitive to the changes in variance than that in the modulation correlations. Our results suggest that the sensitivity of the statistical features in the subcortical levels contributes to the identification and discrimination of natural sound textures.

Slow waves and cognitive output have been modulated in humans by phase-targeted auditory stimulation. However, to advance its technical development and further our understanding, implementation of the method in animal models is indispensable. Here, we report the successful employment of slow waves’ phase-targeted closed-loop auditory stimulation (CLAS) in rats. To validate this new tool both conceptually and functionally, we tested the effects of up- and down-phase CLAS on proportions and spectral characteristics of sleep, and on learning performance in the single-pellet reaching task, respectively. Without affecting 24 hr sleep-wake behavior, CLAS specifically altered delta (slow waves) and sigma (sleep spindles) power persistently over chronic periods of stimulation. While up-phase CLAS does not elicit a significant change in behavioral performance, down-phase CLAS exerted a detrimental effect on overall engagement and success rate in the behavioral test. Overall CLAS-dependent spectral changes were positively correlated with learning performance. Altogether, our results provide proof-of-principle evidence that phase-targeted CLAS of slow waves in rodents is efficient, safe, and stable over chronic experimental periods, enabling the use of this high-specificity tool for basic and preclinical translational sleep research.