scholarly journals The effect of NMDA-R antagonist, MK-801, on neuronal mismatch along the auditory thalamocortical pathway

2019 ◽  
Author(s):  
Gloria G Parras ◽  
Catalina Valdés-Baizabal ◽  
Lauren Harms ◽  
Patricia Michie ◽  
Manuel S Malmierca

ABSTRACTEfficient 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.Significance 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.

2019 ◽  
Author(s):  
Yamil Vidal ◽  
Perrine Brusini ◽  
Michela Bonfieni ◽  
Jacques Mehler ◽  
Tristan Bekinschtein

AbstractAs the evidence of predictive processes playing a role in a wide variety of cognitive domains increases, the brain as a predictive machine becomes a central idea in neuroscience. In auditory processing a considerable amount of progress has been made using variations of the Oddball design, but most of the existing work seems restricted to predictions based on physical features or conditional rules linking successive stimuli. To characterise the predictive capacity of the brain to abstract rules, we present here two experiments that use speech-like stimuli to overcome limitations and avoid common confounds. Pseudowords were presented in isolation, intermixed with infrequent deviants that contained unexpected phoneme sequences. As hypothesized, the occurrence of unexpected sequences of phonemes reliably elicited an early prediction error signal. These prediction error signals do not seemed to be modulated by attentional manipulations due to different task instructions, suggesting that the predictions are deployed even when the task at hand does not volitionally involve error detection. In contrast, the amount of syllables congruent with a standard pseudoword presented before the point of deviance exerted a strong modulation. Prediction error’s amplitude doubled when two congruent syllables were presented instead of one, despite keeping local transitional probabilities constant. This suggest that auditory predictions can be built integrating information beyond the immediate past. In sum, the results presented here further contribute to the understanding of the predictive capabilities of the human auditory system when facing complex stimuli and abstract rules.Significance StatementThe generation of predictions seem to be a prevalent brain computation. In the case of auditory processing this information is intrinsically temporal. The study of auditory predictions has been largely circumscribed to unexpected physical stimuli features or rules connecting consecutive stimuli. In contrast, our everyday experience suggest that the human auditory system is capable of more sophisticated predictions. This becomes evident in the case of speech processing, where abstract rules with long range dependencies are universal. In this article, we present two electroencephalography experiments that use speech-like stimuli to explore the predictive capabilities of the human auditory system. The results presented here increase the understanding of the ability of our auditory system to implement predictions using information beyond the immediate past.


2019 ◽  
Vol 28 (4) ◽  
pp. 834-842
Author(s):  
Harini Vasudevan ◽  
Hari Prakash Palaniswamy ◽  
Ramaswamy Balakrishnan

Purpose The main purpose of the study is to explore the auditory selective attention abilities (using event-related potentials) and the neuronal oscillatory activity in the default mode network sites (using electroencephalogram [EEG]) in individuals with tinnitus. Method Auditory selective attention was measured using P300, and the resting state EEG was assessed using the default mode function analysis. Ten individuals with continuous and bothersome tinnitus along with 10 age- and gender-matched control participants underwent event-related potential testing and 5 min of EEG recording (at wakeful rest). Results Individuals with tinnitus were observed to have larger N1 and P3 amplitudes along with prolonged P3 latency. The default mode function analysis revealed no significant oscillatory differences between the groups. Conclusion The current study shows changes in both the early sensory and late cognitive components of auditory processing. The change in the P3 component is suggestive of selective auditory attention deficit, and the sensory component (N1) suggests an altered bottom-up processing in individuals with tinnitus.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jannath Begum-Ali ◽  
◽  
Anna Kolesnik-Taylor ◽  
Isabel Quiroz ◽  
Luke Mason ◽  
...  

Abstract Background Sensory modulation difficulties are common in children with conditions such as Autism Spectrum Disorder (ASD) and could contribute to other social and non-social symptoms. Positing a causal role for sensory processing differences requires observing atypical sensory reactivity prior to the emergence of other symptoms, which can be achieved through prospective studies. Methods In this longitudinal study, we examined auditory repetition suppression and change detection at 5 and 10 months in infants with and without Neurofibromatosis Type 1 (NF1), a condition associated with higher likelihood of developing ASD. Results In typically developing infants, suppression to vowel repetition and enhanced responses to vowel/pitch change decreased with age over posterior regions, becoming more frontally specific; age-related change was diminished in the NF1 group. Whilst both groups detected changes in vowel and pitch, the NF1 group were largely slower to show a differentiated neural response. Auditory responses did not relate to later language, but were related to later ASD traits. Conclusions These findings represent the first demonstration of atypical brain responses to sounds in infants with NF1 and suggest they may relate to the likelihood of later ASD.


2002 ◽  
Vol 13 (04) ◽  
pp. 188-204 ◽  
Author(s):  
Shigeyuki Kuwada ◽  
Julia S. Anderson ◽  
Ranjan Batra ◽  
Douglas C. Fitzpatrick ◽  
Natacha Teissier ◽  
...  

The scalp-recorded amplitude-modulation following response (AMFR)” is gaining recognition as an objective audiometric tool, but little is known about the neural sources that underlie this potential. We hypothesized, based on our human studies and single-unit recordings in animals, that the scalp-recorded AMFR reflects the interaction of multiple sources. We tested this hypothesis using an animal model, the unanesthetized rabbit. We compared AMFRs recorded from the surface of the brain at different locations and before and after the administration of agents likely to enhance or suppress neural generators. We also recorded AMFRs locally at several stations along the auditory neuraxis. We conclude that the surface-recorded AMFR is indeed a composite response from multiple brain generators. Although the response at any modulation frequency can reflect the activity of more than one generator, the AMFRs to low and high modulation frequencies appear to reflect a strong contribution from cortical and subcortical sources, respectively.


2021 ◽  
Vol 22 (11) ◽  
pp. 6141
Author(s):  
Teodora Larisa Timis ◽  
Ioan Alexandru Florian ◽  
Sergiu Susman ◽  
Ioan Stefan Florian

Aneurysms and vascular malformations of the brain represent an important source of intracranial hemorrhage and subsequent mortality and morbidity. We are only beginning to discern the involvement of microglia, the resident immune cell of the central nervous system, in these pathologies and their outcomes. Recent evidence suggests that activated proinflammatory microglia are implicated in the expansion of brain injury following subarachnoid hemorrhage (SAH) in both the acute and chronic phases, being also a main actor in vasospasm, considerably the most severe complication of SAH. On the other hand, anti-inflammatory microglia may be involved in the resolution of cerebral injury and hemorrhage. These immune cells have also been observed in high numbers in brain arteriovenous malformations (bAVM) and cerebral cavernomas (CCM), although their roles in these lesions are currently incompletely ascertained. The following review aims to shed a light on the most significant findings related to microglia and their roles in intracranial aneurysms and vascular malformations, as well as possibly establish the course for future research.


2020 ◽  
Vol 16 ◽  
pp. 174480692092785 ◽  
Author(s):  
Mayumi Sonekatsu ◽  
Hiroshi Yamada ◽  
Jianguo G Gu

An electrophysiological technique that can record nerve impulses from a single nerve fiber is indispensable for studying modality-specific sensory receptors such as low threshold mechanoreceptors, thermal receptors, and nociceptors. The teased-fiber single-unit recording technique has long been used to resolve impulses that are likely to be from a single nerve fiber. The teased-fiber single-unit recording technique involves tedious nerve separation procedures, causes nerve fiber impairment, and is not a true single-fiber recording method. In the present study, we describe a new and true single-fiber recording technique, the pressure-clamped single-fiber recording method. We have applied this recording technique to mouse whisker hair follicle preparations with attached whisker afferents as well as to skin-nerve preparations made from mouse hindpaw skin and saphenous nerves. This new approach can record impulses from rapidly adapting mechanoreceptors (RA), slowly adapting type 1 mechanoreceptors (SA1), and slowly adapting type 2 mechanoreceptors (SA2) in these tissue preparations. We have also applied the pressure-clamped single-fiber recordings to record impulses on Aβ-fibers, Aδ-fibers, and C-fibers. The pressure-clamped single-fiber recording technique provides a new tool for sensory physiology and pain research.


Neuroreport ◽  
2000 ◽  
Vol 11 (9) ◽  
pp. 2031-2034 ◽  
Author(s):  
Frank Düsterhöft ◽  
Udo Häusler ◽  
Uwe Jürgens

Author(s):  
Luodi Yu ◽  
Jiajing Zeng ◽  
Suiping Wang ◽  
Yang Zhang

Purpose This study aimed to examine whether abstract knowledge of word-level linguistic prosody is independent of or integrated with phonetic knowledge. Method Event-related potential (ERP) responses were measured from 18 adult listeners while they listened to native and nonnative word-level prosody in speech and in nonspeech. The prosodic phonology (speech) conditions included disyllabic pseudowords spoken in Chinese and in English matched for syllabic structure, duration, and intensity. The prosodic acoustic (nonspeech) conditions were hummed versions of the speech stimuli, which eliminated the phonetic content while preserving the acoustic prosodic features. Results We observed language-specific effects on the ERP that native stimuli elicited larger late negative response (LNR) amplitude than nonnative stimuli in the prosodic phonology conditions. However, no such effect was observed in the phoneme-free prosodic acoustic control conditions. Conclusions The results support the integration view that word-level linguistic prosody likely relies on the phonetic content where the acoustic cues embedded in. It remains to be examined whether the LNR may serve as a neural signature for language-specific processing of prosodic phonology beyond auditory processing of the critical acoustic cues at the suprasyllabic level.


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