Cortical Microcircuit Mechanisms of Mismatch Negativity and Its Underlying Subcomponents

Ross, Jordan M.; Hamm, Jordan P.

doi:10.3389/fncir.2020.00013

Cited by 46 publications

(62 citation statements)

References 194 publications

(280 reference statements)

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“…Interestingly, tuned_in units also show strong MM responses [ Figure 4F , STD vs. CTR WT ( P = 1.04e-10) and FX ( P = 1.58e-7); STD vs. DEV WT ( P = 0.0003) and FX ( P = 0.0002), n = 249 and 184 units, Mann–Whitney U test]. This diverges from theories suggesting that enhancement of DEV response is primarily due to the non-adapted units in the local microcircuit (Ross and Hamm, 2020 ). The proportion of tuned_in units was comparable between genotypes ( Supplementary Figure 2 ).…”

Section: Resultsmentioning

confidence: 67%

“…Mismatch responses, on the other hand, were more dependent on the laminar position rather than the tuning preference of units. MM responses were present in the adapted units, suggesting that single units might report mismatch despite strong adaptation levels (Ross and Hamm, 2020 ). L2/3 had the strongest MM responses in WT, but not in FX, where they were equally represented across the cortical column.…”

Section: Discussionmentioning

confidence: 99%

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Impaired Adaptation and Laminar Processing of the Oddball Paradigm in the Primary Visual Cortex of Fmr1 KO Mouse

Pak

Kissinger

Chubykin

2021

Front. Cell. Neurosci.

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Both adaptation and novelty detection are an integral part of sensory processing. Recent animal oddball studies have advanced our understanding of circuitry underlying contextual processing in early sensory areas. However, it is unclear how adaptation and mismatch (MM) responses depend on the tuning properties of neurons and their laminar position. Furthermore, given that reduced habituation and sensory overload are among the hallmarks of altered sensory perception in autism, we investigated how oddball processing might be altered in a mouse model of fragile X syndrome (FX). Using silicon probe recordings and a novel spatial frequency (SF) oddball paradigm, we discovered that FX mice show reduced adaptation and enhanced MM responses compared to control animals. Specifically, we found that adaptation is primarily restricted to neurons with preferred oddball SF in FX compared to WT mice. Mismatch responses, on the other hand, are enriched in the superficial layers of WT animals but are present throughout lamina in FX animals. Last, we observed altered neural dynamics in FX mice in response to stimulus omissions. Taken together, we demonstrated that reduced feature adaptation coexists with impaired laminar processing of oddball responses, which might contribute to altered sensory perception in FX syndrome and autism.

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Section: Resultsmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Impaired Adaptation and Laminar Processing of the Oddball Paradigm in the Primary Visual Cortex of Fmr1 KO Mouse

Pak

Kissinger

Chubykin

2021

Front. Cell. Neurosci.

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“…Some researchers have cited a lack of cellular neurophysiological evidence for this interpretation; instead referring to known properties of sensory neurons, such as stimulus‐specific adaptation (SSA), as possible mechanisms of MMN generation (Jääskeläinen et al., 2004; May & Tiitinen, 2010; Ulanovsky et al., 2003). These two propositions, which are referred to as the memory and adaptation hypotheses of MMN, are not necessarily mutually exclusive, as some researchers have pointed out (Fitzgerald & Todd, 2020; Garrido et al., 2009); although the extent of their relative contributions is unknown, and a description of the mechanism(s) underlying MMN generation remains incomplete (Ross & Hamm, 2020).…”

Section: Introductionmentioning

confidence: 99%

Classical and controlled auditory mismatch responses to multiple physical deviances in anaesthetised and conscious mice

O’Reilly

Conway

2020

Eur J of Neuroscience

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Abbreviations: AEP, auditory evoked potential; DEV CTR , deviant stimulus in the many-standards control paradigm; DEV OD , deviant stimulus in the oddball paradigm; ISI, inter-stimulus interval; MMN, mismatch negativity; MMR, mismatch response; MMR classic , conventional MMR, calculated by DEV OD-STD OD ; MMR control , controlled MMR, calculated by DEV OD-DEV CTR ; N1, first large negative amplitude peak observed in the AEP; P1, first large positive amplitude peak observed in the AEP of conscious mice; P off , positive amplitude peak following stimulus termination; SPL, sound pressure level; SSA, stimulus-specific adaptation; STD control , comparison of STD OD-STD CTR ; STD CTR , standard stimulus in the many-standards control paradigm; STD OD , standard stimulus in the oddball paradigm.

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“…These fast-spiking GABAergic interneurons are thought to be particularly sensitive to NMDAr antagonists, notably because of the cortical excitation observed after acute NMDAr antagonist administration, which is possibly due to a preferential reduction in their firing, resulting in the disinhibition of excitatory pyramidal neurons 56 – 58 . A link between inhibition of GABAergic tone mediated by NMDAr hypofunction on interneurons and glutamatergic hyperexcitation has been proposed in a rat model of NMDAr antagonist repeated exposure 59 , and it has been reported that cortical PV- (along with somatostatin-) positive neurons influence representations of auditory stimuli (see Ross and Hamm for review 60 ). Therefore, the NMDAr hypofunction suggested by the MMN attenuation observed in this study might reflect a probable PCP-induced alteration of PV-positive neurons, which is thought to resemble an aspect of SZ 56 .…”

Section: Discussionmentioning

confidence: 99%

Mismatch negativity as EEG biomarker supporting CNS drug development: a transnosographic and translational study

et al. 2021

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The lack of translation from basic research into new medicines is a major challenge in CNS drug development. The need to use novel approaches relying on (i) patient clustering based on neurobiology irrespective to symptomatology and (ii) quantitative biomarkers focusing on evolutionarily preserved neurobiological systems allowing back-translation from clinical to nonclinical research has been highlighted. Here we sought to evaluate the mismatch negativity (MMN) response in schizophrenic (SZ) patients, Alzheimer’s disease (AD) patients, and age-matched healthy controls. To evaluate back-translation of the MMN response, we developed EEG-based procedures allowing the measurement of MMN-like responses in a rat model of schizophrenia and a mouse model of AD. Our results indicate a significant MMN attenuation in SZ but not in AD patients. Consistently with the clinical findings, we observed a significant attenuation of deviance detection (~104.7%) in rats subchronically exposed to phencyclidine, while no change was observed in APP/PS1 transgenic mice when compared to wild type. This study provides new insight into the cross-disease evaluation of the MMN response. Our findings suggest further investigations to support the identification of neurobehavioral subtypes that may help patients clustering for precision medicine intervention. Furthermore, we provide evidence that MMN could be used as a quantitative/objective efficacy biomarker during both preclinical and clinical stages of SZ drug development.

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Cortical Microcircuit Mechanisms of Mismatch Negativity and Its Underlying Subcomponents

Cited by 46 publications

References 194 publications

Impaired Adaptation and Laminar Processing of the Oddball Paradigm in the Primary Visual Cortex of Fmr1 KO Mouse

Impaired Adaptation and Laminar Processing of the Oddball Paradigm in the Primary Visual Cortex of Fmr1 KO Mouse

Classical and controlled auditory mismatch responses to multiple physical deviances in anaesthetised and conscious mice

Mismatch negativity as EEG biomarker supporting CNS drug development: a transnosographic and translational study

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