Biology subjects

Malmierca, M. S.

Publications and source records attributed to Malmierca, M. S..

9 recordsLinked to original sources

bioRxiv2026

Extended high frequency hearing influences cortical response amplitudes to speech

Since young adults hear sounds up to 20 kHz, the loss of extended high-frequency hearing (EHF; above 8 kHz) is a hallmark of age-related hearing loss, often progressing from early lifetime. However, this deficit frequently goes undetected because routine clinical hearing tests and most hearing aids are currently limited mostly up to 8 kHz. EHF hearing has been linked to deficits in speech perception in noise and to self-reported hearing. However, it remains elusive how EHF hearing influences speech intelligibility. Here we recorded neuromagnetic brain responses using magnetoencephalography (MEG) within a frequency-tagging speech paradigm designed to probe hierarchical levels of attention and memory-dependent speech processing and recognition. Auditory evoked cortical magnetic field (AEF) responses were significantly reduced in both left and right brain hemispheres in individuals with impaired EHF hearing compared to those subjects with rather preserved EHF hearing. A gradual reinforcement of left-hemispheric AEF seen over age was not observed in young adults (19-29 y) with preserved EHF hearing. This was linked to stronger auditory brainstem responses (ABR), reflecting better neural synchronized auditory responses at stimulus onset. The reinforced left hemispheric dominance in young adults with impaired EHF hearing, in contrast, was linked to lower ABRs. Our findings suggest that sound energy above 8 kHz contributes through its impact on stimulus-onset synchrony to phase locking of oscillations in the auditory cortex to intelligible speech. Together, the results highlight the need to reconsider the neglect of EHF hearing in both audiological assessment and hearing aid design. SignificanceWe show here that deficits in extended high-frequency (EHF) hearing, up to now neglected in routine clinical audiometry and hearing aid technology, lead to reduced cortical evoked auditory field (AEF) response amplitudes to attended and unattended speech, even at a young age. A gradual increase in reinforced left-hemispheric AEF responses during attended speech does not occur in young people with good EHF hearing; this is linked to better synchronization of neural responses at the onset of sound. This suggests a crucial role of sounds containing energy above 8kHz in minimizing the need for cognitive resources during active listening. Collectively, our results challenge current clinical practices and underscore the need to incorporate EHF hearing into audiological assessment and hearing aid design.

neuroscience↗

bioRxiv2026

Cortical deviance detection represents a canonical difference signal

Context modulates neural processing of sensory stimuli. Neural responses are suppressed to stimuli that are typical in their context and augmented to stimuli that deviate from their context. The latter has been conceptualized as a "prediction error", which can serve to enhance the salience, direct attention, or support learning about behaviorally relevant events. Predictive coding theories posit that prediction errors act to signal the difference between internal predictions and actual sensory input, yet most paradigms simultaneously alter both predictions and input, so cannot test for a true difference signal. Increased neural responses to deviants could, instead, encode generalized surprise or augmented bottom-up signaling. Here we compare neural responses to auditory stimuli across oddball paradigm variants. We found that responses of putative excitatory neurons in primary auditory cortex (A1) to auditory deviants contain frequency change information and a memory trace of contextual information. Interestingly, in a fixed-deviant oddball paradigm where predictions are altered but deviant input remains constant, neural response patterns encoded standard-to-deviant frequency difference. These results support the interpretation that A1 deviance detection can be interpreted as a sensory prediction error that represents the difference between prediction and sensory input, a corollary of the predictive coding framework.

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bioRxiv2025

Comparison and Dynamic interaction between Auditory Cortex and Prefrontal Cortex of Behaving Monkeys during Novelty Detection

The ability to detect deviations from expected sensory input is fundamental for adaptive behavior. We recorded electrocorticographic activity from the auditory (AC) and prefrontal (PFC) cortices of behaving macaques during an auditory oddball task to probe the cortical dynamics of predictive processing. Repetition of standard stimuli evoked suppression and facilitation in AC and strong low-frequency (2 Hz) enhancement in PFC, accompanied by bidirectional delta-band coupling indicative of a shared predictive state. Deviant stimuli triggered early AC responses followed by PFC activation and increased feedforward and feedback connectivity across delta, theta, and gamma bands. Behavioral engagement amplified both prediction and prediction error signals, strengthening cortical network coordination. Together, these findings reveal a hierarchical predictive network in which the AC encodes sensory regularities and violations, while the PFC integrates predictive context in a behaviorally dependent manner.

neuroscience↗

bioRxiv2025

Responses to oddball communication sequences in the bat frontal and auditory cortices

Stimulus-specific adaptation (SSA) is a ubiquitous phenomenon in the animal kingdom across sensory modalities, but this type of neural response has rarely been studied using natural sounds in the auditory brain. Here, we leveraged the well-documented acoustic repertoire of the bat species Carollia perspicillata to study adaptation in the bat brain using natural communication sounds. We searched for SSA in single neuron spiking activity measured in two brain areas simultaneously: the auditory cortex and the frontal auditory field. The stimuli consisted of natural distress syllables, a form of vocalization produced by bats under duress. Bat distress vocalizations signal different degrees of urgency based on their amplitude modulation pattern, without large differences in their spectral structure. These distress vocalizations make an ideal test case for exploring the limits of neural deviance detection when considering naturalistic soundscapes with low stimulus contrast. The results show limited evidence for stimulus-specific adaptation in response to natural sound sequences in the majority of neurons studied. Many neurons did show a prominent effect related to context-dependent changes, caused by the type of sounds that occurred most frequently within each oddball sequence. Context-dependent responses were strongest in frontal neurons. Decoding analysis showed the existence of neural populations in both frontal and auditory cortices, which could distinguish between deviants and standards occurring within the same sequence, without large changes in evoked spike counts. Taken together, our results highlight the diversity of neural mechanisms complementing classical stimulus-specific adaptation when encoding natural vocalizations that do not differ markedly in their spectral composition.

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bioRxiv2024

Cortical state change by auditory deviants: a mismatch response generation mechanism in unconsciousness

Context-dependent sensory processing within the predictive coding framework relies on detecting mismatches between incoming stimuli and internal predictive models. Sensory deviants elicit prediction errors, seen as enhanced neural responses, that update these models and influence attention and behaviour. Although prediction errors have been widely observed across brain regions, the downstream processes remain poorly understood. In this study, we recorded electrocorticography in 5 urethane-anaesthetised rats and identified cortical slow oscillations, characterised by spontaneous transitions between "Up" and "Down" states. Deviant stimuli in an auditory oddball paradigm evoked an initial positive prediction error, followed by a prolonged, all-or-nothing response which spread in a travelling wave across the cortex. Identified as putative evoked cortical Up states, these responses were not evoked by standards, omissions or a many-standards control. Up states following deviants occurred more recently after a previous Up state when compared to spontaneous Up states. In preliminary data from an awake rat, long-latency Up states were not present spontaneously or evoked. In a different rat, anaesthetic depth was key to spontaneous and evoked Up states, with more robust Up/Down states and more reliable triggering of Up states under deeper anaesthesia. These results suggest that sensory deviants may cause shifts in cortical state under anaesthesia, explaining the long-latency MMR under anaesthesia and sleep. HighlightsO_LIWhat is the central question of this study? Whether long-latency deviant-evoked mismatch responses could be produced by deviant stimuli in the oddball paradigm evoking Up states. C_LIO_LIWhat is the main finding and its importance? In anaesthetised rat, responses to unexpected stimuli show two components, an early mismatch negativity followed by an Up state, that may be related to deviant activation of cortical ensembles by unexpected stimuli. C_LI

neuroscience↗

bioRxiv2023

Acetylcholine Modulates the Precision of Prediction Error in the Auditory Cortex

A fundamental property of sensory systems is their ability to detect novel stimuli in the ambient environment. The auditory brain contains neurons that decrease their response to repetitive sounds but increase their firing rate to novel or deviant stimuli; the difference between both responses is known as stimulus-specific adaptation or neuronal mismatch (nMM). Here, we tested the effect of microiontophoretic applications of ACh on the neuronal responses in the auditory cortex (AC) of anesthetized rats during an auditory oddball paradigm, including cascade controls. Results indicate that ACh modulates the nMM, affecting prediction error responses but not repetition suppression, and this effect is manifested predominantly in infragranular cortical layers. The differential effect of ACh on responses to standards, relative to deviants (in terms of averages and variances), were consistent with the representational sharpening that accompanies an increase in the precision of prediction errors. These findings suggest that ACh plays an important role in modulating prediction error signaling in the AC and gating the access of these signals to higher cognitive levels.

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bioRxiv2019

Dopamine gates prediction error forwarding in the cortices of the inferior colliculus

The predictive processing framework describes perception as a hierarchical predictive model of sensation. Higher-level neural structures constrain the processing at lower-level structures by suppressing synaptic activity induced by predictable sensory input. But when predictions fail, deviant input is forwarded bottom-up as prediction error to update the perceptual model. The earliest prediction error signals identified in the auditory pathway emerge from the nonlemniscal inferior colliculus (IC). The drive that these feedback signals exert on the perceptual model depends on their expected precision, which determines the postsynaptic gain applied in prediction error forwarding. Expected precision is theoretically encoded by the neuromodulatory (e.g., dopaminergic) systems. To test this empirically, we recorded extracellular responses from the rat nonlemniscal IC to oddball and cascade sequences before, during and after the microiontophoretic application of dopamine or eticlopride (a D2-like receptor antagonist). Hence, we studied dopaminergic modulation on the subcortical processing of unpredictable and predictable auditory changes. Results demonstrate that dopamine reduces the net neuronal responsiveness exclusively to unexpected input, without significantly altering the processing of expected auditory events at population level. We propose that, in natural conditions, dopaminergic projections from the thalamic subparafascicular nucleus to the nonlemniscal IC could serve as a precision-weighting mechanism mediated by D2-like receptors. Thereby, the levels of dopamine release in the nonlemniscal IC could modulate the early bottom-up flow of prediction error signals in the auditory system by encoding their expected precision.

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bioRxiv2019

Prediction errors explain mismatch signals of neurons in the medial prefrontal cortex

The mismatch negativity (MMN) is a key biomarker of automatic deviance detection thought to emerge from two cortical sources. First, the auditory cortex (AC) encodes spectral regularities and reports frequency-specific deviances. Then, more abstract representations in the prefrontal cortex (PFC) allow to detect contextual changes of potential behavioral relevance. However, the precise location and time asynchronies between neuronal correlates underlying this fronto-temporal network remain unclear and elusive. Our study presented auditory oddball paradigms along with no-repetition controls to record mismatch responses in neuronal spiking activity and local field potentials at the rat medial PFC. Whereas mismatch responses in the auditory system are mainly induced by stimulus-dependent effects, we found that auditory responsiveness in the PFC was driven by unpredictability, yielding context-dependent, comparatively delayed, more robust and longer-lasting mismatch responses mostly comprised of prediction error signaling activity. This characteristically different composition discarded that mismatch responses in the PFC could be simply inherited or amplified downstream from the auditory system. Conversely, it is more plausible for the PFC to exert top-down influences on the AC, since the PFC exhibited flexible and potent predictive processing, capable of suppressing redundant input more efficiently than the AC. Remarkably, the time course of the mismatch responses we observed in the spiking activity and local field potentials of the AC and the PFC combined coincided with the time course of the large-scale MMN-like signals reported in the rat brain, thereby linking the microscopic, mesoscopic and macroscopic levels of automatic deviance detection.

neuroscience↗

bioRxiv2019

The effect of NMDA-R antagonist, MK-801, on Neuronal Mismatch along the Auditory Thalamocortical System

Efficient sensory processing requires that the brain is able to maximize its response to unexpected stimuli, while suppressing responsivity to expected events. Mismatch negativity (MMN) is an auditory event-related potential that occurs when a regular pattern is interrupted by an event that violates the expected properties of the pattern. MMN has been found to be reduced in individuals with schizophrenia in over 100 separate studies, an effect believed to be underpinned by glutamate N-methyl-D-aspartate receptor (NMDA-R) dysfunction, as it is observed that NMDA-R antagonists also reduce MMN in healthy volunteers. The aim of the current study is to examine this effect in rodents. Using single unit recording in specific auditory areas using methods not readily utilized in humans, we have previously demonstrated that neuronal indices of rodent mismatch responses recorded from thalamic and cortical areas of the brain can be decomposed into a relatively simple repetition suppression and a more sophisticated prediction error process. In the current study, we aimed to test how the NMDA-R antagonist, MK-801, affected both of these processes along the rat auditory thalamocortical pathway. We found that MK-801 had the opposite effect than expected, and enhanced thalamic repetition suppression and cortical prediction error. These single unit data correlate with the recordings of local field responses. Together with previous data, this study suggests that our understanding of the contribution of NMDA-R system to MMN generation is far from complete, and also has potential implications for future research in schizophrenia.\n\nSignificance StatementIn this study, we demonstrate that an NMDA-R antagonist, MK-801, differentially affects single neuron responses to auditory stimuli along the thalamocortical axis by increasing the response magnitude of unexpected events in the auditory cortex and intensifying the adaptation of responses to expected events in the thalamus. Thus, we provide evidence that NMDA-R antagonists alter the balance between prediction-error and repetition suppression processes that underlie the generation of mismatch responses in the brain, and these effects are differentially expressed at different levels of auditory processing. As effects of MK-801 were in the opposite direction to our expectations, it demonstrates that our understanding of role of NMDA-R in synaptic plasticity and the neural processes underpinning MMN generation are far from complete.

neuroscience↗