<i>N</i>-methyl <scp>d</scp>-aspartate receptor hypofunction reduces visual contextual integration

Schielke, Alexander; Krekelberg, Bart

doi:10.1167/jov.21.6.9

Cited by 4 publications

(3 citation statements)

References 59 publications

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“…For example, it is unclear whether SS results from an enhanced inhibition or a weakened excitation or both in the neural circuitry [ 3 ]. Some studies suggest that SS is primarily due to a reduction of cortical excitation [ 15 , 94 ], which is consistent with the psychophysical experiment reporting that N-methyl d-aspartate receptor hypofunction reduces visual contextual integration [ 95 ]. However, other studies suggest that SS is caused by alterations of intracortical inhibition [ 16 , 96 – 99 ], and still others show that SS can be affected by top-down influence through a disinhibition mechanism based on the interaction between different types of interneurons and excitatory pyramidal neurons [ 10 , 18 , 100 ].…”

Section: Discussionsupporting

confidence: 73%

Mechanisms of Surround Suppression Effect on the Contrast Sensitivity of V1 Neurons in Cats

et al. 2022

Neural Plasticity

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Surround suppression (SS) is a phenomenon that a neuron’s response to visual stimuli within the classical receptive field (cRF) is suppressed by a concurrent stimulation in the surrounding receptive field (sRF) beyond the cRF. Studies show that SS affects neuronal response contrast sensitivity in the primary visual cortex (V1). However, the underlying mechanisms remain unclear. Here, we examined SS effect on the contrast sensitivity of cats’ V1 neurons with different preferred SFs using external noise-masked visual stimuli and perceptual template model (PTM) analysis at the system level. The contrast sensitivity was evaluated by the inverted threshold contrast of neurons in response to circular gratings of different contrasts in the cRF with or without an annular grating in the sRF. Our results showed that SS significantly reduced the contrast sensitivity of cats’ V1 neurons. The SS-induced reduction of contrast sensitivity was not correlated with SS strength but was dependent on neuron’s preferred SF, with a larger reduction for neurons with low preferred SFs than those with high preferred SFs. PTM analysis of threshold versus external noise contrast (TvC) functions indicated that SS decreased contrast sensitivity by increasing both the internal additive noise and impact of external noise for neurons with low preferred SFs, but improving only internal additive noise for neurons with high preferred SFs. Furthermore, the SS effect on the contrast-response function of low- and high-SF neurons also exhibited different mechanisms in contrast gain and response gain. Collectively, these results suggest that the mechanisms of SS effect on neuronal contrast sensitivity may depend on neuronal populations with different SFs.

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Section: Discussionsupporting

confidence: 73%

Mechanisms of Surround Suppression Effect on the Contrast Sensitivity of V1 Neurons in Cats

et al. 2022

Neural Plasticity

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“…Early human studies showed that high doses of ketamine strongly affected characteristics of eye movements ( Radant et al, 1998 ), and it was subsequently shown that even low doses reproduce some of the abnormalities seen in subjects with schizophrenia, such as reduced eye acceleration during initiation, reduced closed loop gain ( Weiler et al, 2000 ). Injections of subanesthetic dose of ketamine 0.3–0.5 mg/kg in non-human primates reproduce various sensory and cognitive dysfunctions of schizophrenia, such as dysfunction of the visual working memory ( Sawagashira and Tanaka, 2021 ) and impaired visual contextual integration ( Schielke and Krekelberg, 2021 ) in macaques, deficits in executive function in marmosets ( Kotani et al, 2016 ). Recently, it has been reported in marmosets that ketamine also induced disruption of scan paths, with limited effects on saccade motor control during free-viewing of face images ( Selvanayagam et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

The effect of ketamine on eye movement characteristics during free-viewing of natural images in common marmosets

Polyakova

Iwase²,

Hashimoto³

et al. 2022

Front. Neurosci.

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Various eye movement abnormalities and impairments in visual information processing have been reported in patients with schizophrenia. Therefore, dysfunction of saccadic eye movements is a potential biological marker for schizophrenia. In the present study, we used a pharmacological model of schizophrenia symptoms in marmosets and compared the eye movement characteristics of marmosets during free-viewing, using an image set identical to those used for human studies. It contains natural and complex images that were randomly presented for 8 s. As a pharmacological model of schizophrenia symptoms, a subanesthetic dose of ketamine was injected intramuscularly for transient and reversible manipulation. Eye movements were recorded and compared under a ketamine condition and a saline condition as a control. The results showed that ketamine affected eye movement characteristics during free-viewing. Saccades amplitude and scanpath length were significantly reduced in the ketamine condition. In addition, the duration of saccades was longer under the ketamine condition than under the saline condition. A similar tendency was observed for the duration of fixations. The number of saccades and fixations tended to decrease in the ketamine condition. The peak saccades velocity also decreased after ketamine injection whereas there was no difference in the main sequence relationship between saccades amplitude and peak velocity. These results suggest that ketamine affected visual exploration but did not affect the oculomotor aspect of saccades in marmosets, consistent with studies in patients with schizophrenia. Therefore, we conclude that the subanesthetic dose of ketamine is a promising pharmacological model of schizophrenia symptoms in common marmosets and can be used in combination with free-viewing paradigms to establish “translatable markers” for schizophrenia in primates.

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“…In the auditory domain this has led to productive research programs studying auditory evoked potentials (Vohs et al, 2012 ; Nakao and Nakazawa, 2014 ; Kim et al, 2015 ; Shahriari et al, 2016 ; Sivarao et al, 2016 ; Wang et al, 2020 ) but we found no reports investigating visual evoked potentials in animal models of Sz. We recently showed that a subanesthetic dose of the NMDA antagonist ketamine given to a nonhuman primate (NHP) recapitulates specific visual disturbances found in Sz (Schielke and Krekelberg, 2021 ). Given the similarity of visual processing in NHP and humans (Orban et al, 2004 ), and the potential translational value of a matched approach in animals and humans (Konoike et al, 2022 ), we are currently using this NHP model to investigate changes in rhythmic neuronal responses associated with NMDA hypofunction.…”

Section: Discussionmentioning

confidence: 99%

Steady state visual evoked potentials in schizophrenia: A review

Schielke

Krekelberg²

2022

Front. Neurosci.

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Over the past decades, researchers have explored altered rhythmic responses to visual stimulation in people with schizophrenia using steady state visual evoked potentials (SSVEPs). Here we systematically review studies performed between 1954 and 2021, as identified on PubMed. We included studies if they included people with schizophrenia, a control group, reported SSVEPs as their primary outcome, and used quantitative analyses in the frequency domain. We excluded studies that used SSVEPs to primarily quantify cognitive processes (e.g., attention). Fifteen studies met these criteria. These studies reported decreased SSVEPs across a range of frequencies and electrode locations in people living with schizophrenia compared to controls; none reported increases. Null results, however, were common. Given the typically modest number of subjects in these studies, this is consistent with a moderate effect size. It is notable that most studies targeted frequencies that fall within the alpha and beta band, and investigations of frequencies in the gamma band have been rare. We group test frequencies in frequency bands and summarize the results in topographic plots. From the wide range of approaches in these studies, we distill suggested experimental designs and analysis choices for future experiments. This will increase the value of SSVEP studies, improve our understanding of the mechanisms that result in altered rhythmic responses to visual stimulation in schizophrenia, and potentially further the development of diagnostic tools.

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N-methyl d-aspartate receptor hypofunction reduces visual contextual integration

Cited by 4 publications

References 59 publications

Mechanisms of Surround Suppression Effect on the Contrast Sensitivity of V1 Neurons in Cats

Mechanisms of Surround Suppression Effect on the Contrast Sensitivity of V1 Neurons in Cats

The effect of ketamine on eye movement characteristics during free-viewing of natural images in common marmosets

Steady state visual evoked potentials in schizophrenia: A review

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