Publications by authors named "Manuel S Malmierca"

Diverse biological factors, such as sex and age, confer heterogeneity on sensory processing challenges in autism. These factors result in major difficulties in the processing of contextual information in social and non-social situations. To assess divergence in autistic traits, it is critical to consider sex- and age-related variability.

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This article traces the history of auditory neuroscience in Spain. It begins with the pioneering contributions of Santiago Ramón y Cajal, who meticulously described the organization of every region of the auditory system, from the cochlea to the cerebral cortex. His legacy continued with his disciples, Rafael Lorente de Nó, who conducted a detailed study of the cochlear nuclei, and Fernando de Castro, who later passed the baton to Jaime A.

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Under the predictive coding framework, the brain generates a model of the environment based on previous experiences. Incoming sensory information is compared to this model, such that if predictions do not match sensory inputs, a prediction error is generated. Predictions are passed top-down, and prediction errors emerge when bottom-up information does not match the predictions.

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The detection of novel, low probability events in the environment is critical for survival. To perform this vital task, our brain is continuously building and updating a model of the outside world; an extensively studied phenomenon commonly referred to as predictive coding. Predictive coding posits that the brain is continuously extracting regularities from the environment to generate predictions.

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Article Synopsis
  • The research focuses on understanding how the brain detects new or novel stimuli, which is still not fully grasped, particularly regarding its effects on behavior.
  • A protocol is proposed for measuring electrical activity in the auditory cortex of macaque monkeys while they engage in tasks that test their ability to detect novelty.
  • The paper outlines the essential steps for training the monkeys, surgically preparing them, accurately placing electrodes using MRI, and recording their neuronal activity to establish a connection between this activity and their behavior in novelty detection.
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According to the predictive processing framework, perception emerges from the reciprocal exchange of predictions and prediction errors (PEs) between hierarchically organized neural circuits. The nonlemniscal division of the inferior colliculus (IC) is the earliest source of auditory PE signals, but their neuronal generators, properties, and functional relevance have remained mostly undefined. We recorded single-unit mismatch responses to auditory oddball stimulation at different intensities, together with activity evoked by two sequences of alternating tones to control frequency-specific effects.

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The neural mechanisms underlying novelty detection are not well understood, especially in relation to behavior. Here, we present single-unit responses from the primary auditory cortex (A1) from two monkeys trained to detect deviant tones amid repetitive ones. Results show that monkeys can detect deviant sounds, and there is a strong correlation between late neuronal responses (250-350 ms after deviant onset) and the monkeys' perceptual decisions.

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Exposure to brief, intense sound can produce profound changes in the auditory system, from the internal structure of inner hair cells to reduced synaptic connections between the auditory nerves and the inner hair cells. Moreover, noisy environments can also lead to alterations in the auditory nerve or to processing changes in the auditory midbrain, all without affecting hearing thresholds. This so-called hidden hearing loss (HHL) has been shown in tinnitus patients and has been posited to account for hearing difficulties in noisy environments.

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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.

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The relative importance or saliency of sensory inputs depend on the animal's environmental context and the behavioural responses to these same inputs can vary over time. Here we show how freely moving rats, trained to discriminate between deviant tones embedded in a regular pattern of repeating stimuli and different variations of the classic oddball paradigm, can detect deviant tones, and this discriminability resembles the properties that are typical of neuronal adaptation described in previous studies. Moreover, the auditory brainstem response (ABR) latency decreases after training, a finding consistent with the notion that animals develop a type of plasticity to auditory stimuli.

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Prediction provides key advantages for survival, and cognitive studies have demonstrated that the brain computes multilevel predictions. Evidence for predictions remains elusive at the neuronal level because of the complexity of separating neural activity into predictions and stimulus responses. We overcome this challenge by recording from single neurons from cortical and subcortical auditory regions in anesthetized and awake preparations, during unexpected stimulus omissions interspersed in a regular sequence of tones.

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Age-related hearing loss is a widespread condition among the elderly, affecting communication and social participation. Given its high incidence, it is not unusual that individuals suffering from age-related hearing loss also suffer from other age-related neurodegenerative diseases, a scenario which severely impacts their quality of life. Furthermore, recent studies have identified hearing loss as a relevant risk factor for the development of dementia due to Alzheimer's disease, although the underlying associations are still unclear.

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The corticothalamic (CT) pathways emanate from either Layer 5 (L5) or 6 (L6) of the neocortex and largely outnumber the ascending, thalamocortical pathways. The CT pathways provide the anatomical foundations for an intricate, bidirectional communication between thalamus and cortex. They act as dynamic circuits of information transfer with the ability to modulate or even drive the response properties of target neurons at each synaptic node of the circuit.

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The auditory cortex (AC) encompasses distinct fields subserving partly different aspects of sound processing. One essential function of the AC is the detection of unpredicted sounds, as revealed by differential neural activity to predictable and unpredictable sounds. According to the predictive coding framework, this effect can be explained by repetition suppression and/or prediction error signaling.

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The mismatch negativity (MMN) is a key biomarker of automatic deviance detection thought to emerge from 2 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.

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Efficient sensory processing requires that the brain 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. According to the predictive coding framework there are two mechanisms underlying the MMN: repetition suppression and prediction error.

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Dopamine guides behavior and learning through pleasure, according to classic understanding. Dopaminergic neurons are traditionally thought to signal positive or negative prediction errors (PEs) when reward expectations are, respectively, exceeded or not matched. These signed PEs are quite different from the unsigned PEs, which report surprise during sensory processing.

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Auditory deviance detection is a function of the auditory system that allows reduction of the processing demand for repetitive stimuli while stressing unpredictable ones, which are potentially more informative. Deviance detection has been extensively studied in humans using the oddball paradigm, which evokes an event-related potential known as mismatch negativity (MMN). The same stimulation paradigms are used in animal studies that aim to elucidate the neuronal mechanisms underlying deviance detection.

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The inferior colliculus is an auditory structure where inputs from multiple lower centers converge, allowing the emergence of complex coding properties of auditory information such as stimulus-specific adaptation. Stimulus-specific adaptation is the adaptation of neuronal responses to a specific repeated stimulus, which does not entirely generalize to other new stimuli. This phenomenon provides a mechanism to emphasize saliency and potentially informative sensory inputs.

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Mismatch negativity (MMN) is an electrophysiological signature that occurs in response to unexpected stimuli. It is often referred to as a measure of memory-based change detection, because the elicitation of a prediction error response relies on the formation of a prediction, which in turn, is dependent upon intact memory of previous auditory stimulation. As such, the MMN is altered in conditions in which memory is affected, such as Alzheimer's disease, schizophrenia and healthy aging.

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A 'pattern alternation paradigm' has been previously used in human ERP recordings to investigate the brain encoding of complex auditory regularities, but prior studies on regularity encoding in animal models to examine mechanisms of adaptation of auditory neuronal responses have used primarily oddball stimulus sequences to study stimulus-specific adaptation alone. In order to examine the sensitivity of neuronal adaptation to expected and unexpected events embedded in a complex sound sequence, we used a similar patterned sequence of sounds. We recorded single unit activity and compared neuronal responses in the rat inferior colliculus (IC) to sound stimuli conforming to pattern alternation regularity with those to stimuli in which occasional sound repetitions violated that alternation.

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