Activity In Auditory Cortex Research Articles

Layer-specific representation of long-lasting sustained activity in the rat auditory cortex

In the auditory system, distinct and reproducible transient activities responding to the onset of sound have long been the focus when characterizing the auditory cortex, i.e., tonotopic maps, subregions, and layer-specific representation. There is limited information on sustained activities because the rapid adaptation impairs reproducibility and the signal-to-noise ratio. We recently overcame this problem by focusing on neural synchrony and machine learning demonstrated that band-specific power and the phase locking value (PLV) represent sound information in a tonotopic and region-specific manner. Here, we attempted to reveal the layer-specific representation of sustained activities. A microelectrode array recorded sustained activities from layers 2/3, 4, and 5/6 of the rat auditory cortex. We characterized band-specific power and PLV patterns and applied sparse logistic regression (SLR) to discriminate (1) between the sound-induced and spontaneous activities and (2) five test frequencies from the sound-induced activities in each layer. SLR achieved the highest discrimination performance in high-gamma activities in layers 4 and 5/6, higher than in layer 2/3, indicating poor sound representation in layer 2/3. Moreover, the recording sites that contributed to the discrimination in layers 4 and 5/6 had a characteristic frequency similar to the test frequency and were often located in the belt area, indicating tonotopic and region-specific representation. These results indicate that information processing of sustained activities may depend on high-gamma oscillators, i.e., cortical inhibitory interneurons, and reflects layer-specific thalamocortical and corticocortical neural circuits in the auditory system, which may contribute to associative information processing beyond sound frequency in auditory perception.

Self-directed down-regulation of auditory cortex activity mediated by real-time fMRI neurofeedback augments attentional processes, resting cerebral perfusion, and auditory activation

In this work, we investigated the use of real-time functional magnetic resonance imaging (fMRI) with neurofeedback training (NFT) to teach volitional down-regulation of the auditory cortex (AC) using directed attention strategies as there is a growing interest in the application of fMRI-NFT to treat neurologic disorders. Healthy participants were separated into two groups: the experimental group received real feedback regarding activity in the AC; the control group was supplied sham feedback yoked from a random participant in the experimental group and matched for fMRI-NFT experience. Each participant underwent five fMRI-NFT sessions. Each session contained 2 neurofeedback runs where participants completed alternating blocks of “rest” and “lower” conditions while viewing a continuously-updated bar representing AC activation and listening to continuous noise. Average AC deactivation was extracted from each closed-loop neuromodulation run and used to quantify the control over AC (AC control), which was found to significantly increase across training in the experimental group. Additionally, behavioral testing was completed outside of the MRI on sessions 1 and 5 consisting of a subjective questionnaire to assess attentional control and two quantitative tests of attention. No significant changes in behavior were observed; however, there was a significant correlation between changes in AC control and attentional control. Also, in a neural assessment before and after fMRI-NFT, AC activity in response to continuous noise stimulation was found to significantly decrease across training while changes in AC resting perfusion were found to be significantly greater in the experimental group. These results may be useful in formulating effective therapies outside of the MRI, specifically for chronic tinnitus which is often characterized by hyperactivity of the primary auditory cortex and altered attentional processes. Furthermore, the modulation of attention may be useful in developing therapies for other disorders such as chronic pain.

Cortical recruitment determines learning dynamics and strategy

Salience is a broad and widely used concept in neuroscience whose neuronal correlates, however, remain elusive. In behavioral conditioning, salience is used to explain various effects, such as stimulus overshadowing, and refers to how fast and strongly a stimulus can be associated with a conditioned event. Here, we identify sounds of equal intensity and perceptual detectability, which due to their spectro-temporal content recruit different levels of population activity in mouse auditory cortex. When using these sounds as cues in a Go/NoGo discrimination task, the degree of cortical recruitment matches the salience parameter of a reinforcement learning model used to analyze learning speed. We test an essential prediction of this model by training mice to discriminate light-sculpted optogenetic activity patterns in auditory cortex, and verify that cortical recruitment causally determines association or overshadowing of the stimulus components. This demonstrates that cortical recruitment underlies major aspects of stimulus salience during reinforcement learning.

Multi-sensory Gamma Stimulation Ameliorates Alzheimer’s-Associated Pathology and Improves Cognition

We previously reported that inducing gamma oscillations with a non-invasive light flicker (gamma entrainment using sensory stimulus or GENUS) impacted pathology in the visual cortex of Alzheimer's disease mouse models. Here, we designed auditory tone stimulation that drove gamma frequency neural activity in auditory cortex (AC) and hippocampal CA1. Seven days of auditory GENUS improved spatial and recognition memory and reduced amyloid in AC and hippocampus of 5XFAD mice. Changes in activation responses were evident in microglia, astrocytes, and vasculature. Auditory GENUS also reduced phosphorylated tau in the P301S tauopathy model. Furthermore, combined auditory and visual GENUS, but not either alone, produced microglial-clustering responses, and decreased amyloid in medial prefrontal cortex. Whole brain analysis using SHIELD revealed widespread reduction of amyloid plaques throughout neocortex after multi-sensory GENUS. Thus, GENUS can be achieved through multiple sensory modalities with wide-ranging effects across multiple brain areas to improve cognitive function.

Human olfactory-auditory integration requires phase synchrony between sensory cortices

Multisensory integration is particularly important in the human olfactory system, which is highly dependent on non-olfactory cues, yet its underlying neural mechanisms are not well understood. In this study, we use intracranial electroencephalography techniques to record neural activity in auditory and olfactory cortices during an auditory-olfactory matching task. Spoken cues evoke phase locking between low frequency oscillations in auditory and olfactory cortices prior to odor arrival. This phase synchrony occurs only when the participant’s later response is correct. Furthermore, the phase of low frequency oscillations in both auditory and olfactory cortical areas couples to the amplitude of high-frequency oscillations in olfactory cortex during correct trials. These findings suggest that phase synchrony is a fundamental mechanism for integrating cross-modal odor processing and highlight an important role for primary olfactory cortical areas in multisensory integration with the olfactory system.

Neural Variability Limits Adolescent Skill Learning.

Skill learning is fundamental to the acquisition of many complex behaviors that emerge during development. For example, years of practice give rise to perceptual improvements that contribute to mature speech and language skills. While fully honed learning skills might be thought to offer an advantage during the juvenile period, the ability to learn actually continues to develop through childhood and adolescence, suggesting that the neural mechanisms that support skill learning are slow to mature. To address this issue, we asked whether the rate and magnitude of perceptual learning varies as a function of age as male and female gerbils trained on an auditory task. Adolescents displayed a slower rate of perceptual learning compared with their young and mature counterparts. We recorded auditory cortical neuron activity from a subset of adolescent and adult gerbils as they underwent perceptual training. While training enhanced the sensitivity of most adult units, the sensitivity of many adolescent units remained unchanged, or even declined across training days. Therefore, the average rate of cortical improvement was significantly slower in adolescents compared with adults. Both smaller differences between sound-evoked response magnitudes and greater trial-to-trial response fluctuations contributed to the poorer sensitivity of individual adolescent neurons. Together, these findings suggest that elevated sensory neural variability limits adolescent skill learning.SIGNIFICANCE STATEMENT The ability to learn new skills emerges gradually as children age. This prolonged development, often lasting well into adolescence, suggests that children, teens, and adults may rely on distinct neural strategies to improve their sensory and motor capabilities. Here, we found that practice-based improvement on a sound detection task is slower in adolescent gerbils than in younger or older animals. Neural recordings made during training revealed that practice enhanced the sound sensitivity of adult cortical neurons, but had a weaker effect in adolescents. This latter finding was partially explained by the fact that adolescent neural responses were more variable than in adults. Our results suggest that one mechanistic basis of adult-like skill learning is a reduction in neural response variability.

Does airborne ultrasound lead to activation of the auditory cortex?

As airborne ultrasound can be found in many technical applications and everyday situations, the question as to whether sounds at these frequencies can be heard by human beings or whether they present a risk to their hearing system is of great practical relevance. To objectively study these issues, the monaural hearing threshold in the frequency range from 14 to 24 kHz was determined for 26 test subjects between 19 and 33 years of age using pure tone audiometry. The hearing threshold values increased strongly with increasing frequency up to around 21 kHz, followed by a range with a smaller slope toward 24 kHz. The number of subjects who could respond positively to the threshold measurements decreased dramatically above 21 kHz. Brain activation was then measured by means of magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) and with acoustic stimuli at the same frequencies, with sound pressure levels (SPLs) above and below the individual threshold. No auditory cortex activation was found for levels below the threshold. Although test subjects reported audible sounds above the threshold, no brain activity was identified in the above-threshold case under current experimental conditions except at the highest sensation level, which was presented at the lowest test frequency.

A comparison of neural responses in the primary auditory cortex, amygdala, and medial prefrontal cortex of cats during auditory discrimination tasks.

Discriminating biologically relevant sounds is crucial for survival. The neurophysiological mechanisms that mediate this process must register both the reward significance and the physical parameters of acoustic stimuli. Previous experiments have revealed that the primary function of the auditory cortex (AC) is to provide a neural representation of the acoustic parameters of sound stimuli. However, how the brain associates acoustic signals with reward remains unresolved. The amygdala (AMY) and medial prefrontal cortex (mPFC) play keys role in emotion and learning, but it is unknown whether AMY and mPFC neurons are involved in sound discrimination or how the roles of AMY and mPFC neurons differ from those of AC neurons. To examine this, we recorded neural activity in the primary auditory cortex (A1), AMY, and mPFC of cats while they performed a Go/No-go task to discriminate sounds with different temporal patterns. We found that the activity of A1 neurons faithfully coded the temporal patterns of sound stimuli; this activity was not affected by the cats' behavioral choices. The neural representation of stimulus patterns decreased in the AMY, but the neural activity increased when the cats were preparing to discriminate the sound stimuli and waiting for reward. Neural activity in the mPFC did not represent sound patterns, but it showed a clear association with reward and was modulated by the cats' behavioral choices. Our results indicate that the initial auditory representation in A1 is gradually transformed into a stimulus-reward association in the AMY and mPFC to ultimately generate a behavioral choice. NEW & NOTEWORTHY We compared the characteristics of neural activities of primary auditory cortex (A1), amygdala (AMY), and medial prefrontal cortex (mPFC) while cats were performing the same auditory discrimination task. Our results show that there is a gradual transformation of the neural code from a faithful temporal representation of the stimulus in A1, which is insensitive to behavioral choices, to an association with the predictive reward in AMY and mPFC, which, to some extent, is correlated with the animal's behavioral choice.

Neural Correlates of Enhanced Audiovisual Processing in the Bilingual Brain

Bilingualism is associated with enhancements in perceptual and cognitive processing necessary for juggling multiple languages. Recent psychophysical studies demonstrate bilinguals also show enhanced multisensory processing and more restricted temporal binding windows for integrating audiovisual information. Here, we probed the neural mechanisms of bilinguals’ audiovisual benefits. We recorded neuroelectric responses in mono- and bi-lingual listeners to the double-flash paradigm in which auditory beeps concurrent with a single visual flash induces the perceptual illusion of multiple flashes. Relative to monolinguals, bilinguals showed less susceptibility to the illusion (fewer false perceptual reports) coupled with stronger and faster event-related potentials to audiovisual information. Source analyses of EEG data revealed monolinguals’ increased propensity for erroneously perceiving audiovisual stimuli was attributed to increased activity in primary visual (V1) and auditory cortex (PAC), increases in multisensory association areas (BA 37), but reduced frontal activity (BA 10). Regional activations were associated with an opposite pattern of behaviors: whereas stronger V1 and PAC activity predicted slower behavioral responses, stronger frontal BA10 responses elicited faster judgments. Our results suggest bilinguals’ higher precision in audiovisual perception reflects more veridical sensory coding of physical cues coupled with superior top-down gating of sensory information to suppress the generation of false percepts. Findings underscore that the plasticity afforded by speaking multiple languages shapes extra-linguistic brain regions and can enhance audiovisual brain processing in a domain-general manner.

Targeted Cortical Manipulation of Auditory Perception

Driving perception by direct activation of neural ensembles in cortex is a necessary step for achieving a causal understanding of the perceptual code and developing central sensory rehabilitation methods. Here, using optogenetic manipulations during an auditory discrimination task in mice, we show that auditory cortex can be short-circuited by coarser pathways for simple sound identification. Yet, when the sensory decision becomes more complex, involving temporal integration of information, auditory cortex activity is required for sound discrimination and targeted activation of specific cortical ensembles changes perceptual decisions as predicted by our readout of the cortical code. Hence, auditory cortex representations contribute to sound discriminations by refining decisions from parallel routes.

Functional connectivity of PAG with core limbic system and laryngeal cortico-motor structures during human phonation

Previous studies in animals and humans suggest the periaqueductal grey region (PAG) is a final integration station between the brain and laryngeal musculature during phonation. To date, a limited number of functional magnetic neuroimaging (fMRI) studies have examined the functional connectivity of the PAG during volitional human phonation. An event-related, stimulus-induced, volitional movement paradigm was used to examine neural activity during sustained vocalization in neurologically healthy adults and was compared to controlled exhalation through the nose. The contrast of vocalization greater than controlled expiration revealed activation of bilateral auditory cortex, dorsal and ventral laryngeal motor areas (dLMA and vLMA) (p < 0.05, corrected), and suggested activation of the cerbellum, insula, dorsomedial prefrontal cortex (dmPFC), amygdala, and PAG. The functionally defined PAG cluster was used as a seed region for psychophysiological interaction analysis (PPI) to identify regions with greater functional connectivity with PAG during volitional vocalization, while the above functionally defined amygdala cluster was used in an ROI PPI analysis. Whole-brain results revealed increased functional connectivity of the PAG with left vLMA during voicing, relative to controlled expiration, while trend-level evidence was observed for increased PAG/amygdala coupling during voicing (p = 0.07, uncorrected). Diffusion tensor imaging (DTI) analysis confirmed structural connectivity between PAG and vLMA. The present study sheds further light on neural mechanisms of volitional vocalization that include multiple inputs from both limbic and motor structures to PAG. Future studies should include investigation of how these neural mechanisms are affected in individuals with voice disorders during volitional vocalization.

Sound identity is represented robustly in auditory cortex during perceptual constancy

Perceptual constancy requires neural representations that are selective for object identity, but also tolerant across identity-preserving transformations. How such representations arise in the brain and support perception remains unclear. Here, we study tolerant representation of sound identity in the auditory system by recording neural activity in auditory cortex of ferrets during perceptual constancy. Ferrets generalize vowel identity across variations in fundamental frequency, sound level and location, while neurons represent sound identity robustly across acoustic variations. Stimulus features are encoded with distinct time-courses in all conditions, however encoding of sound identity is delayed when animals fail to generalize and during passive listening. Neurons also encode information about task-irrelevant sound features, as well as animals’ choices and accuracy, while population decoding out-performs animals’ behavior. Our results show that during perceptual constancy, sound identity is represented robustly in auditory cortex across widely varying conditions, and behavioral generalization requires conserved timing of identity information.

Interaction of the effects associated with auditory-motor integration and attention-engaging listening tasks

A number of previous studies have implicated regions in posterior auditory cortex (AC) in auditory-motor integration during speech production. Other studies, in turn, have shown that activation in AC and adjacent regions in the inferior parietal lobule (IPL) is strongly modulated during active listening and depends on task requirements. The present fMRI study investigated whether auditory-motor effects interact with those related to active listening tasks in AC and IPL. In separate task blocks, our subjects performed either auditory discrimination or 2-back memory tasks on phonemic or nonphonemic vowels. They responded to targets by either overtly repeating the last vowel of a target pair, overtly producing a given response vowel, or by pressing a response button. We hypothesized that the requirements for auditory-motor integration, and the associated activation, would be stronger during repetition than production responses and during repetition of nonphonemic than phonemic vowels. We also hypothesized that if auditory-motor effects are independent of task-dependent modulations, then the auditory-motor effects should not differ during discrimination and 2-back tasks. We found that activation in AC and IPL was significantly modulated by task (discrimination vs. 2-back), vocal-response type (repetition vs. production), and motor-response type (vocal vs. button). Motor-response and task effects interacted in IPL but not in AC. Overall, the results support the view that regions in posterior AC are important in auditory-motor integration. However, the present study shows that activation in wide AC and IPL regions is modulated by the motor requirements of active listening tasks in a more general manner. Further, the results suggest that activation modulations in AC associated with attention-engaging listening tasks and those associated with auditory-motor performance are mediated by independent mechanisms.

Auditory predictions shape the neural responses to stimulus repetition and sensory change

Perception is a highly active process relying on the continuous formulation of predictive inferences using short-term sensory memory templates, which are recursively adjusted based on new input. According to this idea, earlier studies have shown that novel stimuli preceded by a higher number of repetitions yield greater novelty responses, indexed by larger mismatch negativity (MMN). However, it is not clear whether this MMN memory trace effect is driven by more adapted responses to prior stimulation or rather by a heightened processing of the unexpected deviant, and only few studies have so far attempted to characterize the functional neuroanatomy of these effects. Here we implemented a modified version of the auditory frequency oddball paradigm that enables modeling the responses to both repeated standard and deviant stimuli. Fifteen subjects underwent functional magnetic resonance imaging (fMRI) while their attention was diverted from auditory stimulation. We found that deviants with longer stimulus history of standard repetitions yielded a more robust and widespread activation in the bilateral auditory cortex. Standard tones repetition yielded a pattern of response entangling both suppression and enhancement effects depending on the predictability of upcoming stimuli. We also observed that regularity encoding and deviance detection mapped onto spatially segregated cortical subfields. Our data provide a better understanding of the neural representations underlying auditory repetition and deviance detection effects, and further support that perception operates through the principles of Bayesian predictive coding.

Specialized neural dynamics for verbal and tonal memory: fMRI evidence in congenital amusia.

Behavioral and neuropsychological studies have suggested that tonal and verbal short-term memory are supported by specialized neural networks. To date however, neuroimaging investigations have failed to confirm this hypothesis. In this study, we investigated the hypothesis of distinct neural resources for tonal and verbal memory by comparing typical nonmusician listeners to individuals with congenital amusia, who exhibit pitch memory impairments with preserved verbal memory. During fMRI, amusics and matched controls performed delayed-match-to-sample tasks with tones and words and perceptual control tasks with the same stimuli. For tonal maintenance, amusics showed decreased activity in the right auditory cortex, inferior frontal gyrus (IFG) and dorso-lateral-prefrontal cortex (DLPFC). Moreover, they exhibited reduced right-lateralized functional connectivity between the auditory cortex and the IFG during tonal encoding and between the IFG and the DLPFC during tonal maintenance. In contrasts, amusics showed no difference compared with the controls for verbal memory, with activation in the left IFG and left fronto-temporal connectivity. Critically, we observed a group-by-material interaction in right fronto-temporal regions: while amusics recruited these regions less strongly for tonal memory than verbal memory, control participants showed the reversed pattern (tonal > verbal). By benefitting from the rare condition of amusia, our findings suggest specialized cortical systems for tonal and verbal short-term memory in the human brain.

Reduced cortical thickness in Heschl's gyrus as an in vivo marker for human primary auditory cortex

The primary auditory cortex (PAC) is located in the region of Heschl's gyrus (HG), as confirmed by histological, cytoarchitectonical, and neurofunctional studies. Applying cortical thickness (CTH) analysis based on high-resolution magnetic resonance imaging (MRI) and magnetoencephalography (MEG) in 60 primary school children and 60 adults, we investigated the CTH distribution of left and right auditory cortex (AC) and primary auditory source activity at the group and individual level. Both groups showed contoured regions of reduced auditory cortex (redAC) along the mediolateral extension of HG, illustrating large inter-individual variability with respect to shape, localization, and lateralization. In the right hemisphere, redAC localized more within the medial portion of HG, extending typically across HG duplications. In the left hemisphere, redAC was distributed significantly more laterally, reaching toward the anterolateral portion of HG. In both hemispheres, redAC was found to be significantly thinner (mean CTH of 2.34 mm) as compared to surrounding areas (2.99 mm). This effect was more dominant in the right hemisphere rather than in the left one. Moreover, localization of the primary component of auditory evoked activity (P1), as measured by MEG in response to complex harmonic sounds, strictly co-localized with redAC. This structure-function link was found consistently at the group and individual level, suggesting PAC to be represented by areas of reduced cortex in HG. Thus, we propose reduced CTH as an in vivo marker for identifying shape and localization of PAC in the individual brain.

Hemispheric decoupling of awareness-related activity in human auditory cortex under informational masking and divided attention

Whether unattended sound streams reach perceptual awareness, and the extent to which they are represented in the central auditory system, are fundamental questions of modern hearing science. We examined these questions utilizing M/EEG, multi-tone masking, and a dual-task dichotic listening paradigm. Listeners performed a demanding primary task in one ear—detecting isochronous target-tone streams embedded in random multi-tone backgrounds and counting within-target-stream deviants—and retrospectively reported their awareness of similar masker-embedded targets in the other ear. Irrespective of attention or stimulation ear, left-AC activity strongly covaried with target-stream detection starting as early as 50 ms post-stimulus. In contrast, right-AC activity, while highly sensitive to stimulation ear, was unmodulated by detection until later, and then only weakly. Thus, under certain conditions, human ACs can functionally decouple, such that one—here, right—is automatic and stimulus-driven while the other—here, left—supports perceptual and/or task demands, including basic perceptual awareness of nonverbal sounds both within and outside the focus of top-down selective attention.

From behavior to physiology and back again: The role of auditory cortex in vocal production and control

Vocal communication plays an important role in the lives of both humans and many animal species. Ensuring accurate communication, however, requires auditory self-monitoring to control vocal production and rapidly compensate for errors in vocal output. Despite the importance of this process, the underlying neural mechanisms are relatively unknown. Previous work has demonstrated that neurons in the auditory cortex are suppressed during vocal production, while simultaneously maintaining their sensitivity to vocal feedback, suggesting a role in auditory self-monitoring. The behavioral role of auditory cortex in vocal control, however, remains unclear. We investigated the function of auditory cortical activity during vocal self-monitoring and feedback-dependant vocal control in marmoset monkeys. Using real-time frequency-shifted feedback during vocalization, we demonstrate that marmosets exhibit rapid compensatory changes in vocal production, a feedback-dependent behavior that is predicted by the activities of neurons in auditory cortex. We further establish the role of auditory cortex in vocal control using electrical microstimulation to evoke rapid changes in produced vocalizations. These findings suggest a causal role for the auditory cortex in vocal self-monitoring and feedback-dependent vocal control, linking mechanisms of production and perception, and have important implications for understanding human speech motor control.

Neuronal correlates of auditory streaming in the auditory cortex of behaving monkeys.

This study tested the hypothesis that spiking activity in the primary auditory cortex of monkeys is related to auditory stream formation. Evidence for this hypothesis was previously obtained in animals that were passively exposed to stimuli and in which differences in the streaming percept were confounded with differences between the stimuli. In this study, monkeys performed an operant task on sequences that were composed of light flashes and tones. The tones alternated between a high and a low frequency and could be perceived either as one auditory stream or two auditory streams. The flashes promoted either a one-stream percept or a two-stream percept. Comparison of different types of sequences revealed that the neuronal responses to the alternating tones were more similar when the flashes promoted auditory stream integration, and were more dissimilar when the flashes promoted auditory stream segregation. Thus our findings show that the spiking activity in the monkey primary auditory cortex is related to auditory stream formation.

Not All Predictions Are Equal: "What" and "When" Predictions Modulate Activity in Auditory Cortex through Different Mechanisms.

Using predictions based on environmental regularities is fundamental for adaptive behavior. While it is widely accepted that predictions across different stimulus attributes (e.g., time and content) facilitate sensory processing, it is unknown whether predictions across these attributes rely on the same neural mechanism. Here, to elucidate the neural mechanisms of predictions, we combine invasive electrophysiological recordings (human electrocorticography in 4 females and 2 males) with computational modeling while manipulating predictions about content ("what") and time ("when"). We found that "when" predictions increased evoked activity over motor and prefrontal regions both at early (∼180 ms) and late (430-450 ms) latencies. "What" predictability, however, increased evoked activity only over prefrontal areas late in time (420-460 ms). Beyond these dissociable influences, we found that "what" and "when" predictability interactively modulated the amplitude of early (165 ms) evoked responses in the superior temporal gyrus. We modeled the observed neural responses using biophysically realistic neural mass models, to better understand whether "what" and "when" predictions tap into similar or different neurophysiological mechanisms. Our modeling results suggest that "what" and "when" predictability rely on complementary neural processes: "what" predictions increased short-term plasticity in auditory areas, whereas "when" predictability increased synaptic gain in motor areas. Thus, content and temporal predictions engage complementary neural mechanisms in different regions, suggesting domain-specific prediction signaling along the cortical hierarchy. Encoding predictions through different mechanisms may endow the brain with the flexibility to efficiently signal different sources of predictions, weight them by their reliability, and allow for their encoding without mutual interference.SIGNIFICANCE STATEMENT Predictions of different stimulus features facilitate sensory processing. However, it is unclear whether predictions of different attributes rely on similar or different neural mechanisms. By combining invasive electrophysiological recordings of cortical activity with experimental manipulations of participants' predictions about content and time of acoustic events, we found that the two types of predictions had dissociable influences on cortical activity, both in terms of the regions involved and the timing of the observed effects. Further, our biophysical modeling analysis suggests that predictability of content and time rely on complementary neural processes: short-term plasticity in auditory areas and synaptic gain in motor areas, respectively. This suggests that predictions of different features are encoded with complementary neural mechanisms in different brain regions.